Sepsis with liver dysfunction and coagulopathy predicts an inflammatory pattern of macrophage activation
Renee R. Anderko, Hernando Gómez, Scott Canna, Bita Shakoory, Derek C. Angus, Donald M. Yealy, David T. Huang, John A. Kellum, Joseph A. Carcillo, For the ProCESS Investigators, Derek C. Angus, Amber E. Barnato, Tammy L. Eaton, Elizabeth Gimbel, David T. Huang, Christopher Keener, John A. Kellum, Kyle Landis, Francis Pike, Diana K. Stapleton, Lisa A. Weissfeld, Michael Willochell, Kourtney A. Wofford, Donald M. Yealy, Erik Kulstad, Hannah Watts, Arvind Venkat, Peter C. Hou, Anthony F. Massaro, Siddharth Parmar, Alexander T. Limkakeng, Kori L. Brewer, Theodore R. Delbridge, Allison Mainhart, Lakhmir S. Chawla, James R. Miner, Todd L. Allen, Colin K. Grissom, Stuart P. Swadron, Steven A. Conrad, Richard Carlson, Frank LoVecchio, Ednan K. Bajwa, Michael R. Filbin, Blair A. Parry, Timothy J. Ellender, Andrew E. Sama, Jonathan Fine, Soheil Nafeei, Thomas E. Terndrup, Margaret Wojnar, Ronald G. Pearl, Scott T. Wilber, Richard Sinert, David J. Orban, Jason Wilson, Jacob W. Ufberg, Timothy Albertson, Edward A. Panacek, Sohan Parekh, Scott R. Gunn, Jon S. Rittenberger, Richard J. Wadas, Andrew R. yEdwards, Matthew Kelly, Henry E. Wang, T. Holmes, Michael T. McCurdy, Craig Weinert, Estelle S. Harris, Wesley H. Self, Carolyn Phillips, Ronald M. Migues
Abstract
BACKGROUND: Interleukin-1 receptor antagonists can reduce mortality in septic shock patients with hepatobiliary dysfunction and disseminated intravascular coagulation (HBD + DIC), an organ failure pattern with inflammatory features consistent with macrophage activation. Identification of clinical phenotypes in sepsis may allow for improved care. We aim to describe the occurrence of HBD + DIC in a contemporary cohort of patients with sepsis and determine the association of this phenotype with known macrophage activation syndrome (MAS) biomarkers and mortality. We performed a retrospective nested case-control study in adult septic shock patients with concurrent HBD + DIC and an equal number of age-matched controls, with comparative analyses of all-cause mortality and circulating biomarkers between the groups. Multiple logistic regression explored the effect of HBD + DIC on mortality and the discriminatory power of the measured biomarkers for HBD + DIC and mortality. RESULTS: Six percent of septic shock patients (n = 82/1341) had HBD + DIC, which was an independent risk factor for 90-day mortality (OR = 3.1, 95% CI 1.4-7.5, p = 0.008). Relative to sepsis controls, the HBD + DIC cohort had increased levels of 21 of the 26 biomarkers related to macrophage activation (p < 0.05). This panel was predictive of both HBD + DIC (sensitivity = 82%, specificity = 84%) and mortality (sensitivity = 92%, specificity = 90%). CONCLUSION: The HBD + DIC phenotype identified patients with high mortality and a molecular signature resembling that of MAS. These observations suggest trials of MAS-directed therapies are warranted.