Lung Biology in Health & Disease Volume 215 Ventilator-Induced Lung Injury

This reference surveys current best practices in the prevention and management of ventilator-induced lung injury (VILI) and spans the many pathways and mechanisms of VILI including cell injury and repair, the modulation of alveolar-capillary barrier properties, and lung and systemic inflammatory consequences of injurous mechanical ventilation. Considering many emerging therapeutic options, this guide also reviews the wide array of clinical studies on lung protection strategies and approaches to ARDS patients at risk for VILI. Doody Review Services Reviewer: David J. Dries, MD(University of Minnesota Medical School) Description: This comprehensive review of an important clinical topic is a volume in the Lung Biology in Health and Disease series. Purpose: Basic research, clinical consequences, and ongoing questions in ventilator-induced lung injury are presented. Audience: Fellows and senior practitioners in multidisciplinary critical care medicine are an appropriate audience for this work. Editors and authors represent an international group providing seminal contributions to the understanding of this problem. Features: Initial chapters include reviews of mechanical stress and hemodynamic and microcirculatory changes in the ventilated lung. These chapters set the stage for a review of mediators and mechanical/biological signal transduction and a discussion of the role for these factors in ventilator-induced lung injury. After cytokines and genomic aspects are reviewed, recent clinical trials and their implications for bedside management are discussed. Concluding chapters offer reviews of high frequency ventilation, clinical trial design, and imaging as a means to better understand interaction of the ventilator and lung. The 28 chapters are clearly written line drawings and black-and-white photographs reproduce with good quality. Each review contains an extensive reference list with emphasis on primary work dating to within two to three years of publication. The table of contents includes chapters, authorship, and major subheadings while a subject index of approximately 20 pages provides adequate access to content. Assessment: The recent expansion in our understanding of ventilator-induced lung injury is one of the most important recent developments in cardiopulmonary critical care. This book reviews not only the exciting clinical developments in this area, it also provides an excellent overview of the physiology and molecular biology of this problem. The list of authors is a who's who of contributors in this area. Introduction......Page 14 Preface......Page 16 Contributors......Page 18 Contents......Page 24 I. Introduction......Page 36 II. Mechanical Forces......Page 37 III. Membrane Signal Transduction......Page 41 IV. Intracellular Signal Transduction......Page 45 V. Conclusion......Page 49 References......Page 50 I. Introduction......Page 56 II. Determinants of Regional Pressure and Volume in Health and Disease......Page 57 III. Micromechanics of the Normal Lung......Page 61 IV. Alveolar Micromechanics in Injury States......Page 64 V. Mechanisms by Which Ventilators Injure Lungs......Page 67 VI. Concluding Remarks......Page 72 References......Page 73 I. Introduction......Page 80 II. The Histology of VILI......Page 81 III. Cellular Stress Failure in Ventilator-Injured Lungs......Page 83 IV. Determinants of PM Tension......Page 85 V. Cell Deformation–Associated PM Remodeling......Page 87 VI. PM Repair......Page 90 VII. Effects of PM Wounding on Gene Expression and Cell Survival......Page 92 References......Page 94 I. Introduction......Page 104 II. Passive Effects of Lung Distention......Page 106 III. Active Endothelial Control of Vascular Permeability......Page 107 References......Page 121 I. Introduction......Page 132 II. Effect of Pulmonary Expansion on the Pulmonary Vascular Tree......Page 133 III. Response of the Endothelial Cell to Shear Forces......Page 135 IV. Interactions Between Airway and Pulmonary Vascular Pressures......Page 136 V. Mechanisms Disrupting the Blood–Gas Barrier......Page 138 VI. Behavior of Airway and Vascular Pressures in Heterogeneous Areas......Page 140 VII. Role of Vascular Pressure and Flow on Genesis of VILI......Page 141 VIII. Effect of Respiratory Rate and Flow on Expression of VILI......Page 142 IX. Cyclic Effect on the Microvascular Environment Induced by Mechanical Ventilation......Page 145 X. Effect of Postalveolar Vascular Pressure on the Development of VILI......Page 146 XI. Potential Clinical Implications......Page 147 XII. Conclusions......Page 148 References......Page 149 I. Introduction......Page 154 II. Acute Pulmonary Edema Consecutive to High-Lung-Volume Ventilation......Page 155 III. Respiratory Mechanics and Severity of VILI......Page 163 IV. Respiratory System PV Curve Changes During Lung Injury......Page 164 V. Improvement of Lung Mechanical Properties and Protection from VILI......Page 178 VI. Clinical Considerations......Page 180 References......Page 182 I. Introduction......Page 192 II. Background......Page 193 III. Introduction to Pulmonary Fluid–Structure Interactions......Page 197 IV. Microscale Fluid–Structure Interactions Leading to VILI......Page 205 V. The Protective Effect of Pulmonary Surfactant......Page 220 VI. Future Directions......Page 228 References......Page 232 I. Introduction......Page 240 II. Ventilator-Induced Lung Inflammation......Page 241 III. Cells Submitted to Mechanical Stress......Page 243 V. Mechanosensing......Page 244 VII. Cyclic Stretch–Induced Cell Activation......Page 246 VIII. Synergy Between Cyclic Stretch and Inflammatory Stimuli......Page 247 IX. Genes Activated by Cyclic Stretch......Page 248 X. Conclusions and Perspectives......Page 250 References......Page 251 I. Introduction......Page 258 II. Mechanical Ventilation of the ALI/ARDS Lung......Page 259 IV. Cytokines and the Pathogenesis of VALI/VILI......Page 260 V. The Role of TNF-α During the Pathogenesis of VALI/VILI......Page 262 VI. The Role of IL-1β During the Pathogenesis of VALI/VILI......Page 270 VII. The Role of IL-6 During the Pathogenesis of VALI/VILI......Page 273 VIII. The Role of IFN-γ During the Pathogenesis of VALI/VILI......Page 274 IX. The Role of IL-10 During the Pathogenesis of VALI/VILI......Page 275 X. The Role of TGF-β During the Pathogenesis of VALI/VILI......Page 276 XI. The Role of Chemokines and Chemokine Receptors During the Pathogenesis of VALI/VILI......Page 277 XII. The Role of CC Chemokines During the Pathogenesis of VALI/VILI......Page 281 XIII. Conclusion......Page 282 References......Page 284 I. Introduction......Page 302 II. Physiological Effects of MV......Page 304 III. Mechanical Strain–Induced Release of Inflammatory Mediators In Vitro......Page 305 IV. Pulmonary and Systemic Release of Inflammatory Mediators in Ex Vivo and In Vivo Models of VILI......Page 306 V. Passage of Mediators from Lung to Bloodstream......Page 308 VII. Bacterial Translocation in MV......Page 310 IX. Pulmonary and Systemic Inflammatory Mediators in VILI in Clinical Studies......Page 311 XI. Conclusions......Page 313 References......Page 314 I. Introduction......Page 320 II. Alveolar Epithelial Sodium Transport......Page 321 III. Alveolar Fluid Reabsorption During VILI......Page 322 References......Page 323 I. Introduction......Page 328 II. Surfactant Depletion and Deactivation......Page 329 III. Toxic Lung Injuries......Page 332 IV. Inflammation and Infection: The Importance of Lung Priming and the Two-Hit Theory......Page 337 VI. Counteracting Previous Lung Injury......Page 341 VII. Clinical Considerations......Page 344 References......Page 345 I. Introduction......Page 350 II. Rationale for Biological Markers of VILI......Page 351 III. Recent Progress in Identifying Biological Markers of VILI......Page 353 IV. Future Approaches to Identifying Markers of VILI......Page 365 V. Summary and Conclusions......Page 368 References......Page 369 I. Introduction—Historical Context......Page 376 II. Hypercapnia—Definitions and Terminology......Page 377 III. Hypercapnia—Physiologic Effects......Page 380 IV. Acute Organ Injury: Evidence That CO[sub(2)] Is Protective......Page 382 V. Mechanisms of CO[sub(2)]-Induced Protection......Page 391 VI. Molecular Mechanisms of Hypercapnia-Induced Tissue Injury......Page 395 VII. Administration and Dose Response......Page 397 VIII. Role of Buffering......Page 398 IX. Hypercapnia—Clinical Studies......Page 400 X. Future Directions......Page 401 References......Page 402 I. Introduction......Page 412 II. Effects of Mechanical Ventilation on Alveolar Epithelial Barrier Function......Page 414 III. Alveolar Epithelial Ion and Fluid Transport......Page 420 IV. Effects of Mechanical Strain on Epithelial Inflammatory Mediators......Page 422 V. Consequences of the Loss of Epithelial Barrier Function......Page 426 VI. Effects of VILI on Surfactants......Page 427 VII. Summary......Page 428 References......Page 429 I. Introduction—VALI and Genome Medicine......Page 438 II. Challenges to Unraveling the Genetics of VALI......Page 439 III. Current Status of VALI/VILI Genetics and the Candidate Gene Approach......Page 441 IV. Gene Expression in Animal Models of VILI......Page 443 V. Ortholog Gene Database in VALI and Mechanical Stress......Page 447 VI. Regional Heterogeneity in Ventilator-Associated Mechanical Stress......Page 448 VII. Pre-B-Cell Colony–Enhancing Factor as an ALI Candidate Gene......Page 453 VIII. Preliminary PBEF Genotyping in ALI Patients......Page 455 IX. Preliminary IL-6 Genotyping in VALI......Page 457 X. Summary......Page 458 References......Page 459 I. Introduction......Page 466 II. Histological Evidence of Mechanical Ventilation–Induced Lung Distortion/Overinflation......Page 467 III. CT Evidence of Mechanical Ventilation–Induced Lung Distortion/Overinflation......Page 471 References......Page 477 I. Introduction......Page 482 II. Anatomic Imaging of VILI: Quantifying Edema Accumulation......Page 483 III. Functional Imaging of VILI......Page 491 IV. Molecular Imaging of VILI......Page 496 References......Page 503 I. Introduction......Page 510 II. MV and the Cytokine Network......Page 511 III. Modulation of the Cytokine Network in ALI: Evidence from Studies......Page 514 IV. Impact of MV on the Cytokine Network in Healthy Lungs......Page 524 References......Page 527 I. Introduction......Page 532 II. Traditional Approach to MV in ALI/ARDS......Page 533 III. Mechanisms of VILI......Page 534 IV. Lung-Protective Ventilation......Page 535 V. Clinical Trials of Lung-Protective MV Strategies......Page 538 VI. Controversies......Page 544 VII. Summary......Page 548 References......Page 549 I. Introduction......Page 554 II. Randomized, Controlled Trials of Tidal Volume Reduction in ARDS......Page 556 III. Meta-Analyses of the RCTs of Tidal Volume Reduction During ARDS......Page 562 IV. Impact of the Low Tidal Volume Trials on Practice Patterns......Page 567 V. Conclusions......Page 568 References......Page 569 I. Introduction......Page 572 II. Experimental Scientific Principles......Page 576 III. Computerized Protocol Experience......Page 610 IV. Summary......Page 624 References......Page 626 I. Introduction......Page 646 II. Understanding Current Practice......Page 648 III. Do We Know Why Clinicians Do Not Follow Practice Guidelines?......Page 650 IV. Barriers to Changing Practice in the ICU......Page 651 V. Models of Changing Clinical Practice......Page 653 VII. Conclusions......Page 656 References......Page 657 I. Introduction—Questions to Be Addressed......Page 662 II. Inclusion and Exclusion Criteria......Page 666 III. Outcomes......Page 667 IV. Study Designs......Page 669 V. The RCT......Page 670 VI. Ethical Issues in a Clinical Trial......Page 673 VII. Understanding the Results of a Clinical Trial......Page 679 VIII. Nonrandomized Cohort Studies......Page 680 IX. Evidence-Based Medicine and Hierarchy of Study Designs......Page 683 References......Page 684 II. Perfluorocarbon Liquids as Media for Breathing......Page 690 III. Effects of Perfluorocarbons on Inflammation and Oxidative Injury......Page 691 IV. In Vitro Effects of Neat Perfluorocarbon Liquids Involving Surface Tension......Page 695 V. Effects of Ventilation with Perfluorocarbons on Lung Injury......Page 696 VI. Mechanical Protection from Lung Injury by Perfluorocarbon Ventilation......Page 700 References......Page 703 I. Introduction—The Pulmonary Surfactant System......Page 712 II. Surfactant Alterations and Replacement Treatment in ALI/ARDS......Page 716 III. Role of the Pulmonary Surfactant System in VILI......Page 719 IV. Conclusions......Page 724 References......Page 725 I. Introduction......Page 732 II. Background......Page 733 III. Rationale for HFOV......Page 734 IV. Clinical Experience with HFOV......Page 739 V. Future Directions in the Application of HFOV......Page 740 References......Page 742 II. Gene Therapy for ALI......Page 746 IV. Conclusions......Page 751 References......Page 752 A......Page 756 B......Page 757 C......Page 758 E......Page 760 F......Page 761 H......Page 762 I......Page 763 L......Page 764 M......Page 765 N......Page 766 P......Page 767 R......Page 769 S......Page 770 T......Page 771 V......Page 772 Z......Page 773