1;Table of Contents;52;List of Contributors;113;Common Abbreviations;284;I Genomics and Proteomics;294.1;Rethinking Sepsis: New Insights from Gene Expression Profiling Studies;304.1.1;Introduction;304.1.2;How to Identify and Measure Heterogeneity;304.1.3;Sources of Heterogeneity in Sepsis Patients;314.1.4;New Insights from Gene-expression Studies;324.1.5;Genomic Heterogeneity;344.1.6;Further Questions on an Existing Sepsis Model;364.1.7;Functional Mapping of Sepsis Genome to Monitor Immune Function;374.1.8;Conclusion;394.1.9;References;394.2;Mitochondrial Genetics and Sepsis;414.2.1;Introduction;414.2.2;Oxidative Phosphorylation and ATP Generation;414.2.3;Reactive Oxygen Species;424.2.4;Apoptosis;424.2.5;Mitochondria and Sepsis;434.2.6;Mitochondrial Genetics;434.2.7;Mitochondrial Haplogroups;444.2.8;Conclusion;474.2.9;References;474.3;Lung Proteomics in Intensive Care;504.3.1;Introduction;504.3.2;The Search for Biomarkers;504.3.3;Lung Proteomics;524.3.4;Applications in ALI/ARDS;584.3.5;Future Directions;594.3.6;References;625;II Inflammatory Response;645.1;The Host Response to Sepsis;655.1.1;Introduction;655.1.2;Epidemiology and Genetic Variability;665.1.3;Pathogen Recognition Systems;675.1.4;Coagulation and Anticoagulation;705.1.5;Immune Suppression and Apoptosis;725.1.6;HMGB1 and RAGE;725.1.7;The Cholinergic Anti-inflammatory Pathway;735.1.8;Macrophage Migration Inhibitory Factor;745.1.9;C5a and C5a Receptor;745.1.10;Conclusion;745.1.11;References;745.2;Endotoxin Tolerance: Mechanisms and Clinical Applicability;775.2.1;Introduction;775.2.2;Mechanisms of Endotoxin Tolerance;775.2.3;Endothelial Function and Microcirculation during LPS Tolerance;795.2.4;Clinical Applicability and Therapeutic Possibilities;815.2.5;Conclusions;825.2.6;References;825.3;Oxidative Stress and Endothelial Dysfunction during Sepsis;855.3.1;Introduction;855.3.2;Sources and Actions of ROS and RNS in the Endothelium during Sepsis;855.3.3;Mechanisms of Endothelial Dysfunction during Sepsis;875.3.4;Conclusion;895.3.5;References;905.4;Measurement of Carbon Monoxide: From Bench to Bedside;915.4.1;Introduction;915.4.2;Carbon Monoxide Measurement;915.4.3;Carbon Monoxide Concentrations in Critically Ill Patients;925.4.4;Carbon Monoxide Concentrations and Lung Diseases;965.4.5;Carbon Monoxide Concentrations and Other Diseases;1035.4.6;Conclusion;1035.4.7;References;1035.5;Monitoring Immune Dysfunction in Septic Patients: Toward Tailored Immunotherapy;1075.5.1;Introduction;1075.5.2;Monocyte Dysfunction;1085.5.3;T Lymphocyte Dysfunction;1115.5.4;Conclusion;1145.5.5;References;1156;III Current and Future Management of Sepsis;1176.1;Source Control in the ICU;1186.1.1;Introduction;1186.1.2;What is 'Source Control'?;1186.1.3;Elements of Source Control;1196.1.4;Do we need to perform Source Control?;1206.1.5;When to Perform Source Control?;1216.1.6;The Role of the Intensivist;1216.1.7;What if Source Control is Impossible or Fails?;1236.1.8;Special Considerations in Critically Ill Patients;1236.1.9;Conclusion;1256.1.10;References;1256.2;IgM-enriched Immunoglobulins in Sepsis;1276.2.1;Introduction;1276.2.2;Mechanisms of Action of IVIG in Sepsis;1286.2.3;Differences between IgG- and IgM-enriched Immunoglobulins;1296.2.4;Clinical Significance of IgM-enriched IVIG;1306.2.5;Conclusion;1336.2.6;References;1346.3;Clarithromycin: A Promising Immunomodulator in Sepsis;1366.3.1;Introduction;1366.3.2;Indirect Evidence for an Immunomodulatory effect of Macrolides in Pneumonia;1376.3.3;Lessons from Animal Studies;1386.3.4;Conclusion;1416.3.5;References;1426.4;High-flow Hemofiltration as an Adjunctive Therapy in Sepsis;1446.4.1;Introduction;1446.4.2;Mechanism of Action: Hemofiltration as a New Shield against the 'Chaos Theory' and 'Complex Non-linear Systems' in Sepsis;1446.4.3;Recent Animal Trials and Clinical studies Highlighting the Crucial Roles of Dosing and Timing ;1466.4.4;Practic