James A. Russell and Keith R. Walley Am. J. Resp. Crit. Care Med. Jun 15, 2013, vol. 187, no. 12: 1303-1307
Pivotal sepsis clinical trials and preclinical research in 2012 are reviewed. For interventions ranging from synthetic complex starch solutions to recombinant human activated protein C, large multicenter randomized controlled trials generally failed to show benefit and some even demonstrated harm in the intervention group.
In smaller innovative clinical trials simple interventions such as external cooling to control fever and biomarker-guided weaning from mechanical ventilation found potential benefit. Biomarkers for sepsis, including multimarker panels, are increasingly showing promise for clinical application. Breakthroughs in basic research in sepsis continue to highlight the complexity of the systemic inflammatory response and its consequences. A series of publications in AJRCCM follow the septic inflammatory response starting from intracellular structures and organelles to mitochondria and the cytoskeleton. Additional publications explore the key leukocyte subsets acting in sepsis, highlighting the underappreciated role of helper T-cell type 2–related pathways. Cellular remnants in the form of microparticles contribute to coagulopathy and further organ dysfunction. As a consequence, we suggest that sepsis may be the paradigm disease or condition requiring personalized care first to discover and validate new therapies and second to increase survival.