Sepsis is the leading cause of death in critically ill patientsin the United States. Sepsis develops in 750,000 people annually,and more than 210,000 of them die.1,2 After numerous unsuccessfultrials of antiinflammatory agents in patients with sepsis, investigatorsdoubted that mortality could be decreased. Advances in unravelingthe pathophysiology and genetic basis for the host responseto sepsis have changed the prevailing understanding of the syndrome,and several therapies have demonstrated surprising efficacy.In this article, we examine evolving concepts of sepsis anddiscuss new and potential therapies.
A Disorder Due to Uncontrolled Inflammation?
The prevailing theory has been that sepsis represents an uncontrolled. . . [Full Text of this Article]
Failure of the Immune System?
Mechanisms of Immune Suppression in Sepsis
A Shift to Antiinflammatory Cytokines
Anergy
Death of Immune Cells
Reappraisal of Lewis Thomas's Theory
Host Genetic Factors
Surprising Insights about Neutrophils
Lessons from Autopsy Studies
Cellular Hibernation as a Mechanism of Organ Dysfunction
Death of Patients with Sepsis
New Concepts in the Treatment of Sepsis
Activated Protein C
Intensive Insulin Therapy for Hyperglycemia
Volume Resuscitation
Corticosteroids
An Emerging Concept of the Nature of the Immune Response in Sepsis
Potential Therapies for Sepsis
Conclusions
Source Information
From the Departments of Anesthesiology (R.S.H.), Medicine (R.S.H., I.E.K.), and Surgery (R.S.H.), Washington University School of Medicine, St. Louis.
Address reprint requests to Dr. Hotchkiss at the Department of Anesthesiology, Washington University School of Medicine, Campus Box 8054, St. Louis, MO 63110, or at hotch@morpheus.wustl.edu.
Related Letters:
Sepsis — Theory and Therapies
Ronco C., Bellomo R., Lonneman G., Agarwal P. K., Kumari R., Netea M. G., Van der Meer J. W., Kullberg B. J., Hotchkiss R. S., Karl I. E.
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N Engl J Med 2003;
348:1600-1602, Apr 17, 2003.
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