Cover

Contents

Preface

Endotoxemia: Pathophysiological Background

Endotoxin in the Pathogenesis of Sepsis

Abstract

Sepsis: A Conceptual History

How Do Microorganisms Evoke a Response in the Host?

Endotoxin and Sepsis: What Is the Connection?

Conclusions

References

Endotoxins and Other Sepsis Triggers

Abstract

Endotoxin, Microbial Mediators and the Recognition of Sepsis

Microbial Virulence and the Causative Microorganisms of Sepsis

The Role of Bacterial Endotoxin

The Inflammation-Coagulation Networks

Endotoxin Tolerance (Reprogramming) and Sepsis-Induced Immune Suppression

Recognition of Other Microbial Mediators by Pattern Recognition Receptors

Other Microbial Toxins in Sepsis

Conclusions

References

Extracorporeal Endotoxin Removal: Theory and Technology

Rationale of Extracorporeal Removal of Endotoxin in Sepsis: Theory, Timing and Technique

Abstract

Endotoxemia in Animal and Human Sepsis Models

Cardiovascular Response in Sepsis

Pulmonary Response in Sepsis

Renal Response in Sepsis and Sepsis-Related Acute Kidney Injury

Endotoxemia Is an Important Factor of Morbidity and Mortality in Sepsis

Plasma Levels of LPS and LPS-Binding Protein

Diagnostic and Prognostic Implications of Endotoxemia in Critical Illness

A Targeted Extracorporeal Therapy for Endotoxemia

References

Extracorporeal Removal of Endotoxin: The Polymyxin B-Immobilized Fiber Cartridge

Abstract

Endotoxins and Polymyxin B

How to Design the PL-B-Immobilized Fiber and Cartridge

Safety Evaluation

Performances of PL-B-Immobilized Fiber Cartridge

How It Works

Advantages of Uses of Adsorbent Technology to Remove Endotoxin

Conclusion

References

Mechanisms of Polymyxin B Endotoxin Removal from Extracorporeal Blood Flow: Molecular Interactions

Abstract

Methods

Results and Discussion

Concluding Remarks

Acknowledgments

References

Mechanisms of Polymyxin B Endotoxin Removal from Extracorporeal Blood Flow: Hydrodynamics of Sorption

Abstract

Materials and Methods

Results

Discussion

Concluding Remarks

Acknowledgements

References

Endotoxin Removal in Septic Shock in Clinical Settings

Endotoxin Removal by Polymyxin B Immobilized Cartridge Inactivates Circulating Proapoptotic Factors

Abstract

Apoptosis

Apoptotic Pathways

Apoptotic Effects on Tissue/Organ Function

LPS Activation of Apoptosis

PMX-B Hemoperfusion and Apoptosis

Renal Cytotoxicity

TUNEL Apoptotic Assessment

Caspase Activity

Extrinsic Pathway

Intrinsic Pathway

Additional Nonapoptotic Mechanisms

Supportive Evidence in Animals

Overall Conclusions

References

Polymyxin-B Hemoperfusion and Endotoxin Removal: Lessons from a Review of the Literature

Abstract

A Systematic Review of the Literature

After the Systematic Review

Summary

References

PMX Endotoxin Removal in the Clinical Practice: Results from the EUPHAS Trial

Abstract

Methods

Results

Discussion

References

Early Management of Endotoxemia Using the Endotoxin Activity Assay and Polymyxin B-Based Hemoperfusion

Abstract

Materials and Methods

Results

Discussion

Acknowledgement

References

Endotoxin Activity Level and Septic Shock: A Possible Role for Specific Anti-Endotoxin Therapy?

Abstract

Why Measure Endotoxin? Endotoxin as a Sepsis Biomarker

Endotoxin as a Sepsis Mediator: Target for Antiendotoxin Therapy?

Conclusions

References

Endotoxin Removal: Building the Evidence

Endotoxin Removal: How Far from the Evidence? From EUPHAS to EUPHRATES

Abstract

Treating Sepsis: Importance of Targeting Endotoxin

The Use of PMX-B in Japan

The European Experience

Lessons Learned from Previous Trials and Future Directions

Conclusion

References

Endotoxin Removal: How Far from the Evidence? The EUPHAS 2 Project

Abstract

The EUPHAS Study

The EUPHAS 2 Study

Database Statistical Analysis

Conclusions

References

Author Index

Subject Index