John J. Marini Alain F. Broccard University of Minnesota Regions Hospital Minneapolis / St. Paul

1. Advanced Mechanical Ventilation John J. Marini Alain F. Broccard University of Minnesota Regions Hospital Minneapolis / St. Paul USA

2. Advanced Mechanical Ventilation Outline • Consequences of Elevated Alveolar Pressure • Implications of Heterogeneous Lung Unit Inflation • Adjuncts to Ventilation • Prone Positioning • Recruitment Maneuvers • Difficult Management Problems • Acute Lung Injury • Severe Airflow Obstruction • An Approach to Withdrawing Ventilator Support • Advanced Modes for Implementing Ventilation • Case Scenarios

3. Consequences of Elevated Alveolar Pressure--1 • Mechanical ventilation expands the lungs and chest wall by pressurizing the airway during inflation. The stretched lungs and chest wall develop recoil tension that drives expiration. • Positive pressure developed in the pleural space may have adverse effects on venous return, cardiac output and dead space creation. • Stretching the lung refreshes the alveolar gas, but excessive stretch subjects the tissue to tensile stresses which may exceed the structural tolerance limits of this delicate membrane. • Disrupted alveolar membranes allow gas to seep into the interstitial compartment, where it collects, and migrates toward regions with lower tissue pressures. • Interstitial, mediastinal, and subcutaneous emphysema are frequently the consequences. Less commonly, pneumoperitoneum, pneumothorax, and tension cysts may form. • Rarely, a communication between the high pressure gas pocket and the pulmonary veins generates systemic gas emboli.

4. Partitioning of Alveolar Pressure is a Function of Lung and Chest Wall Compliances Lungs are smaller and pleural pressures are higher when the chest wall is stiff.

5. Hemodynamic Effects of Lung Inflation • Lung inflation by positive pressure causes • Increased pleural pressure and impeded venous return • Increased pulmonary vascular resistance • Compression of the inferior vena cava • Retardation of heart rate increases • These effects are much less obvious in the presence of • Adequate circulating volume • Adequate vascular tone • Spontaneous breathing efforts • Preserved adrenergic responsiveness

6. Hemodynamic Effects of Lung Inflation With Low Lung Compliance, High Levels of PEEP are Generally Well Tolerated.

7. Effect of lung expansion on pulmonary vasculature. Capillaries that are embedded in the alveolar walls undergo compression even as interstitial vessels dilate. The net result is usually an increase in pulmonary vascular resistance, unless recruitment of collapsed units occurs.

8. Conflicting Actions of Higher Airway Pressure • Lung Unit Recruitment and Maintenance of Aerated Volume • Gas exchange • Improved Oxygenation • Distribution of Ventilation • Lung protection • Parenchymal Damage • Airway trauma • Increased Lung Distention • Impaired Hemodynamics • Increased Dead Space • Potential to Increase Tissue Stress …Only If Plateau Pressure Rises

9. Gas Extravasation Barotrauma

10. Diseased Lungs Do Not Fully Collapse, Despite Tension Pneumothorax …and They cannot always be fully “opened” Dimensions of a fully Collapsed Normal Lung

11. Tension Cysts

12. Tidally Phasic Systemic Gas Embolism End-Inspiration End-Expiration

13. Consequences of Elevated Alveolar Pressure--2 • In recent years there has been intense interest in another and perhaps common consequence of excessive inflation pressure--Ventilator-Induced Lung Injury (VILI). • VILI appears to develop either as a result of structural breakdown of the tissue by mechanical forces or by mechano-signaling of inflammation due to repeated application of excessive tensile forces. • Although still controversial, it is generally agreed that damage can result from overstretching of lung units that are already open or from shearing forces generated at the junction of open and collapsed tissue. • Tidally recurrent opening and closure of small airways under high pressure is thought to be important in the generation of VILI. • Prevention of VILI is among the highest priorities of the ICU clinician caring for the ventilated patient and is the purpose motivating adoption of “Lung Protective” ventilation strategies. • Translocation of inflammatory products, bacteria, and even gas may contribute to remote damage in systemic organs and help explain why lung protective strategies are associated with lower risk for morbidity and death.

14. Recognized Mechanisms of Airspace Injury Airway Trauma “Stretch” “Shear”

15. Mechanisms of Ventilator-Induced Lung Injury (VILI) • High airway pressures may injure the lungs by repeated overstretching of open alveoli, by exposing delicate terminal airways to high pressure, or by generating shearing forces that tear fragile tissues. • These latter shearing forces tend to occur as small lung units open and close with each tidal cycle and are amplified when the unit opens only after high pressures are reached. • To avoid VILI, end-inspiratory lung pressure (“plateau”) should be kept from rising too high, and when high plateau pressures are required, sufficient PEEP should be applied to keep unstable lung units from opening and closing with each tidal cycle. • Independent of opening and closure, tissue strain is dramatically amplified at the junctions of open and closed lung units when high alveolar pressures are reached. • Extremely high tissue strains may rip the alveolar gas-blood interface. Repeated application of more moderate strains incite inflammation. • Such factors as breath frequency, micro-vascular pressure, temperature, and body position modify VILI expression.

16. Pathways to VILI End-Expiration ModerateStress/Strain Tidal Forces (Transpulmonary and Microvascular Pressures) ExtremeStress/Strain Rupture Signaling Mechano signaling via integrins, cytoskeleton, ion channels inflammatory cascade Cellular Infiltrationand Inflammation Marini / Gattinoni CCM 2004

17. Microvascular Fracture in ARDS A Portal for Gas & Bacteria? 1  Hotchkiss et al Crit Care Med 2002;

18. The Problem of Heterogeneity • The heterogeneous nature of regional mechanical properties presents major difficulty for the clinician, who must apply only a single pressure or flow profile to the airway opening. • Heterogeneity means that some lung units may be overstretched while others remain airless at the same measured airway pressure. • Finding just the right balance of tidal volume and PEEP to keep the lung as open as possible without generating excessive regional tissue stresses is a major goal of modern practice. • Prone positioning tends to reduce the regional gradients of pleural and trans-pulmonary pressure.

19. Opening Pressure 0 Inflated Small Airway 10-20 cmH2O Collapse Alveolar Collapse 20-60 cmH2O (Reabsorption)  Consolidation Spectrum of Regional Opening Pressures (Supine Position) Superimposed Pressure = Lung Units at Risk for Tidal Opening & Closure (from Gattinoni)

20. Different lung regions may be overstretched or underinflated, even as measures of total lung mechanics appear within normal limits. UPPER LUNG TOTAL LUNG Lung Volume Alveolar Pressure LOWER LUNG

21. Recruitment Parallels Volume As A Function of Airway Pressure Recruitment and Inflation (%) Frequency Distribution of Opening Pressures (%) Airway Pressure (cmH2O)

22. 40 Opening pressure 30 Closing pressure 20 From Crotti et al AJRCCM 2001. 10 0 0 5 10 15 20 25 30 35 40 45 50 Paw [cmH2O] Opening and Closing Pressures in ARDS High pressures may be needed to open some lung units, but once open, many units stay open at lower pressure. 50 %

23. Zone of ↑ Risk

24. Dependent to Non-dependent Progression of Injury

25. Histopathology of VILI Belperio et al, J Clin Invest Dec 2002; 110(11):1703-1716

26. Links Between VILI and MSOF Biotrauma and Mediator De-compartmentalization Slutsky, Chest 116(1):9S-16S

27. Airway Orientation in Supine Position

29. Prone Positioning Evens The Distribution of Pleural & Transpulmonary Pressures

30. Prone Positioning Relieves Lung Compression by the Heart Supine Prone

31. Supine Prone * p<0.05 vs Supine * Proning May Benefit the Most Seriously Ill ARDS Subset 0.5 0.4 0.3 Mortality Rate 0.2 0.1 0.0 > 49 40- 49 31- 40 0 - 31 SAPS II Quartiles of SAPS II

32. Supine Prone * p<0.05 vs Supine * Proning Helped Most in High VT Subgroup At Risk For VILI 0.5 0.4 0.3 Mortality Rate 0.2 0.1 0.0 < 8.2 8.2- 9.7 9.7- 12 > 12 VT/Kg Quartiles of VT /Predicted body weight

33. Less Extensive Collapse But Greater PPLAT 100 R = 100% R = 93% Total Lung Capacity [%] Some potentially recruitable units open only at high pressure R = 81% More Extensive Collapse But Lower PPLAT 60 R = 59% From Pelosi et al AJRCCM 2001 20 R = 22% 0 0 60 20 40 Pressure [cmH2O] R = 0% How Much Collapse Is DangerousDepends on the Plateau

34. Recruiting Maneuvers in ARDS • The purpose of a recruiting maneuver is to open collapsed lung tissue so it can remain open during tidal ventilation with lower pressures and PEEP, thereby improving gas exchange and helping to eliminate high stress interfaces. • Although applying high pressure is fundamental to recruitment, sustaining high pressure is also important. • Methods of performing a recruiting maneuver include single sustained inflations and ventilation with high PEEP .

35. TheoreticalEffect of Sustained Inflation on Tidal Cycling Benefit from a recruiting maneuver is usually transient if PEEP remainsunchanged afterward. VOLUME (% TLC) Rimensberger ICM 2000

36. Three Types of Recruitment Maneuvers S-C Lim, et al Crit Care Med2004

37. How is the Injured Lung Best Recruited? • Prone positioning • Adequate PEEP • Adequate tidal volume (and/or intermittent ‘sighs’?) • Recruiting maneuvers • Minimize edema (?) • Lowest acceptable FiO2 (?) • Spontaneous breathing efforts (?)

38. Severe Airflow Obstruction • A major objective of ventilating patients with severe airflow obstruction is to relieve the work of breathing and to minimize auto-PEEP. • Reducing minute ventilation requirements will help impressively in reducing gas trapping. • When auto-PEEP is present, it has important consequences for hemodynamics, triggering effort and work of breathing. • In patients whose expiratory flows are flow limited during tidal breathing, offsetting auto-PEEP with external PEEP may even the gas distribution and reduce breathing effort.

39. Auto-PEEP Adds To the Breathing Workload The pressure-volume areas correspond to the inspiratory mechanical workloads of auto-PEEP (AP) flow resistance and tidal elastance.

40. Gas Trapping in Severe Airflow Obstruction • Disadvantages the respiratory muscles and increases the work of tidal breathing • Often causes hemodynamic compromise, especially during passive inflation • Raises plateau and mean airway pressures, predisposing to barotrauma • Varies with body position and from site to site within the lung

42. Volume Losses in Recumbent Positions Note that COPD patients lose much less lung volume than normals do, due to gas trapping and need to keep the lungs more inflated to minimize the severity of obstruction. Orthopnea may result.

43. PEEP in Airflow Obstruction • Effects Depend on Type and Severity of Airflow Obstruction • Generally Helpful if PEEP  Original Auto-PEEP • Potential Benefits • Decreased Work of Breathing • Increased VT During PSV or PCV • (?) Improved Distribution of Ventilation • (?) Decreased Dyspnea

44. Inhalation Lung Scans in the Lateral Decubitus Position for a Normal Subject and COPD Patient No PEEP PEEP10 Normal Addition of 10 cm H2O PEEP re-opens dependent airways in COPD COPD

45. Flow Limitation “Waterfall” PEEP

46. Adding PEEP that approximates auto-PEEP may reduce the difference in pressure between alveolus (Palv) and airway opening, thereby lowering the negative pleural(Pes) pressure needed to begin inspiration and trigger ventilation.

47. Adding PEEP Lessens the Heterogeneity of End-expiratory Alveolar Pressures and Even the Distribution of Subsequent Inspiratory Flow.

48. ASTHMA COPD PEEP may offset (COPD) or add to auto-PEEP (Asthma), depending on flow limitation. Note that adding 8 cmH2O PEEP to 10 cmH2O of intrinsic PEEP may either reduce effort (Pes, solid arrow) or cause further hyper-inflation (dashed arrow). Ranieri et al, Clinics in Chest Medicine 1996; 17(3):379-94

49. Conventional Modes of Ventilatory Support The traditional modes of mechanical ventilation—Flow-regulated volume Assist Control (“Volume Control”, AMV, AC)) or Pressure-Targeted Assist Control (“Pressure Control”), Synchronized Intermittent Mandatory Ventilation (SIMV)—with flow or pressure targeted mandatory cycles), Continuously Positive Airway Pressure (CPAP) and Pressure Support can be used to manage virtually any patient when accompanied by adequate sedation and settings well adjusted for the patient’s needs. Their properties are discussed in the “Basic Mechanical Ventilation” unit of this series.

50. Positive Airway Pressure Can Be Either Pressure or Flow Controlled—But Not Both Simultaneously Dependent Variable Set Variable Set Variable Dependent Variable