Sepsis is a serious medical condition caused by a severe systemic inflammatory response to a bacterial, fungal, or viral infection that most commonly affects neonates and the elderly. Advances in understanding the pathophysiology of sepsis have resulted in guidelines for care that have helped reduce the risk of dying from sepsis for both children and older adults. Still, over the past three decades, a large number of clinical trials have been undertaken to evaluate pharmacological agents for sepsis. Unfortunately, all of these trials have failed, with the use of some agents even shown to be harmful. One key issue in these trials was the heterogeneity of the patient population that participated. What has emerged is the need to target therapeutic interventions to the specific patient’s underlying pathophysiological processes, rather than looking for a universal therapy that would be effective in a “typical” septic patient, who does not exist. This review supports the concept that identification of the right biomarkers that can direct therapy and provide timely feedback on its effectiveness will enable critical care physicians to decrease mortality of patients with sepsis and improve the quality of life of survivors.
- Received November 19, 2015.
- Accepted February 5, 2016.
This work was supported by the National Institutes of Health National Institute of Diabetes and Digestive Kidney Diseases [Grant F31 DK104533]; the National Institutes of Health Institute of General Medical Sciences [Grants R01 GM106419 and R01 GM112806]; the National Institutes of Health National Center for Advancing Translational Sciences Clinical and Translational Science Award [Grant UL1-TR000039] and the American Heart Association [15GRNT2508025].
- Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics