Ventilator Induced Lung Injury

Ventilator Induced Lung Injury Barotrauma Volutrauma Stretch Injury Biochemical Injury

Ventilator Induced Lung Injury Barotrauma Air leaking into pleural space Air leaking into interstitial space (PIE) Tearing at Bronchio-Alveolar Junction as lung is recruited and allowed to collapse Most occurs in dependent lung zones (transition zone)

Effect of 45 cmH2O PIP Control 5 min 20 min

Ventilator Induced Lung Injury Stretch Injury Alters capillary transmural pressures Changes in transmural pressure causes breaks in capillary endo and epithelium Increases leak of proteinacious material Promotes Atelectasis

Ventilator Induced Lung Injury Stretch Injury Alveolar Space A-C Membrane

Ventilator Induced Lung Injury Rodents ventilated with three modes: High Pressure (45 cmH2O), High Volume Low Pressure (negative pressure ventilator), High Volume (45 cmH2O), Low Volume (strapped chest and abdomen) Dreyfuss,D ARRD 1988;137:1159

Ventilator Induced Lung Injury Volutrauma Caused by cycling of the lung (change in surface area), independent of pressure required Alters Surfactant function Promotes Atelectasis Increases capillary leak of proteinacious material Dreyfuss,D ARRD 1988;137:1159

Ventilator Induced Lung Injury Hyaline Membrane Disease is not really a disease, it’s the result of volume cycling the lungs CMV produces consolidation, over inflation and hyaline membrane formation HFOV uniformly inflates the lung without hyaline membrane formation Meredith K, JAP 1989; 66:2150

Ventilator Induced Lung Injury Premature baboon model Coalson J. Univ Texas San Antonio

Ventilator Induced Lung Injury Premature baboon model Coalson J. Univ Texas San Antonio

Alveolar Edema and Hyaline Membrane

Hemorrhage and Edema

Adult ARDS HFOV - Caring for the Baby in Adults Baby Lung Sitting on Top of a Consolidated Lung Tidal Volumes of 6-10 ml/kg based on weight Tidal Volumes of 20-50 ml/kg based on open lung units Histology is similar to infant lung injury

Ventilator Induced Lung Injury Adult Acute Respiratory Failure Atelectasis Overdistended airways and alveoli Cellular accumulation Hyaline Membranes Lamy ARRD 1976; 114:267

Ventilator Induced Lung Injury Adult ARDS late stage lung structural changes Enlarged air space Septal destruction Fibrotic lesions

ARDS Pulmonary Injury Sequence Phase 1 Early Exudative Treatment Endo/Epithelial Damage Type 1 Alveolar Cell Injury and/or Loss Capillary Congestion Interstitial/Alveolar Edema, Hemorrhage Protein Accumulation Surfactant Deactivation Atelectasis Hyaline Membrane Formation Inflammatory Cell Migration Volutrauma - Increased Protein Leak, Atelectasis, etc.

ARDS Pulmonary Injury Sequence Phase 2 Proliferative (Day 5-10) Proliferation of Type 2 Cells Fibroblast Migration Interstitial Collagen Formation Increased Dead Space Decreased Compliance Increased Pulmonary Vascular Resistance

ARDS Pulmonary Injury Sequence Phase 3 Fibrotic (Day 10-14) Lung Destruction Emphysematous Changes Fibrosis Pulmonary Vascular Obliteration Chronic Lung Disease

Ventilator Induced Lung Injury Biochemical Injury Biochemical agents (mediators) attack the lung Recruit fibrotic proliferation cells to the lung Atelectasis promotes release of chemical mediators Mediators released in the lung can attack other organ systems Cells Macrophages Endothelial and Epithelial Cells Platelets Neutrophils Mediators Cytokines Leukotrienes PAF (Platelet Activating Factor) Thromboxane TNF (Tumor Necrotizing Factor) Complement Proteins Interleukin-1,8

Ware and Matthay NEJM 342 (18): 1334

Pulmonary Injury Sequence There are two injury zones during mechanical ventilation Low Lung Volume Ventilation tears adhesive surfaces High Lung Volume Ventilation over-distends, resulting in “Volutrauma” The difficulty is finding the “Sweet Spot” Froese AB, Crit Care Med 1997; 25:906

Ventilator Induced Lung Injury Twenty Years of One Year Follow Up of Lung Function (DLCO) in ARDS Survivors Suchyta MR, ERS 1997

Ventilator Induced Lung Injury HFOV with Surfactant as Compared to CMV with Surfactant in the Premature Primate HFOV resulted in Less Radiographic Injury Less Oxygenation Injury Less Alveolar Proteinaceous Debris Jackson C AJRCCM 1994; 150:534

Ventilator Induced Lung Injury High Lung Volume Strategies with HFOV Extended Surfactant Activity Normalized Lamellar Body Phospholipid levels Improved lung mechanics All Conventional Ventilator Strategies Resulted in Death or Decreased Surfactant Performance Froese A, ARRD 1993; 148:569

Ventilator Induced Lung Injury

Ventilator Induced Lung Injury Control animal histology Sugiura M, JAP 1994; 77:1355

Ventilator Induced Lung Injury HFOV animal histology Sugiura M, JAP 1994; 77:1355

Ventilator Induced Lung Injury CMV animal histology Sugiura M, JAP 1994; 77:1355

Ventilator Induced Lung Injury HFOV Stimulates Significantly Less Neutrophil Activity Than CMV Neutrophil Activity Has a Role in the Genisis of ARDS, Releasing Active Oxygen Species, Proteinases and Arachidonic Acid Metabolites. Sugiura M, JAP 1994; 77:1355

Ventilator Induced Lung Injury HFOV produces less inflammatory markers than CMV Imai Y, AJRCCM 1994; 150:1550

Ventilator Induced Lung Injury Activation of alveolar macrophages and pro-inflammatory cytokines play a pivotal role in Ventilator Induced Lung Injury Takata M, AJRCCM 1997; 156:272

Risk Factors for ARDS Trauma Shock Syndromes - Sepsis, Cardiogenic Gastric Aspiration Burns Diffuse Pneumonias Near Drowning Drug Overdose Metabolic Events - Pancreatitis, Uremia Systemic Mediator Release Associated Diseases Disseminated Intravascular Coagulopathy Cardiopulmonary Bypass -- Anaphylaxis Extrapulmonary Infection -- Transfusion Reaction

Lung Inflation Patterns Multi-Scan CT (10 scans/sec) 30 kg Pig Pre Lavage Pressure Control Ventilation Paw 13 cmH2O PEEP 5 cmH2O Weiler N. et al, 1999, personal communication

Lung Inflation Patterns Multi-Scan CT (10 scans/sec) 30 kg Pig Pre Lavage Pressure Control Ventilation Paw 23 cmH2O PEEP 15 cmH2O Weiler N et al, 1999, personal communication

Lung Inflation Patterns Multi-Scan CT (10 scans/sec) 30 kg Pig Post Lavage Pressure Control Ventilation Paw 13 cmH2O PEEP 5 cmH2O Weiler N et al, 1999, personal communication

Lung Inflation Patterns Multi-Scan CT (10 scans/sec) 30 kg Pig Post Lavage Pressure Control Ventilation Paw 23 cmH2O PEEP 15 cmH2O Weiler N et al, 1999, personal communication

Lung Inflation Patterns Multi-Scan CT (10 scans/sec) 30 kg Pig Post Lavage Pressure Control Ventilation Paw 33 cmH2O PEEP 25 cmH2O Weiler N et al, 1999, personal communication

Lung Inflation Patterns Multi-Scan CT (10 scans/sec) 30 kg Pig Post Lavage HFOV Paw 23 cmH2O Weiler N. Heinrichs W, et al 1999

“Open up the lung up and keep it open!” Burkhard Lachmann, 1992