Sepsis with liver dysfunction and coagulopathy predicts an inflammatory pattern of macrophage activation

Renee R Anderko; Hernando Gómez; Scott W Canna; Bita Shakoory; Derek C Angus; Donald M Yealy; David T Huang; John A Kellum; Joseph A Carcillo; ProCESS Investigators

doi:10.1186/s40635-022-00433-y

Sepsis with liver dysfunction and coagulopathy predicts an inflammatory pattern of macrophage activation

Intensive Care Med Exp. 2022 Feb 21;10(1):6. doi: 10.1186/s40635-022-00433-y.

Authors

Renee R Anderko^#¹, Hernando Gómez^#^{2

3}, Scott W Canna^{4

5}, Bita Shakoory⁶, Derek C Angus¹, Donald M Yealy⁷, David T Huang¹, John A Kellum^{1

8}, Joseph A Carcillo^{1

8}; ProCESS Investigators

Collaborators

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 Massaro, Siddharth Parmar, Alexander T Limkakeng Jr, Kori Brewer, Theodore R Delbridge, Allison Mainhart, Lakhmir S Chawla, James R Miner, Todd L Allen, Colin K Grissom, Stuart 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 Terndrup, Margaret Wojnar, Ronald G Pearl, Scott T Wilber, Richard Sinert, David J Orban, Jason W 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, Talmage M Holmes, Michael T McCurdy, Craig Weinert, Estelle S Harris, Wesley H Self, Carolyn A Phillips, Ronald M Migues

Affiliations

¹ Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
² Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA. gomezh@upmc.edu.
³ Center for Critical Care Nephrology, Department of Critical Care Medicine, University of Pittsburgh, School of Medicine, 3550 Terrace Street, 6th floor Scaife Hall, Pittsburgh, PA, 15261, USA. gomezh@upmc.edu.
⁴ RK Mellon Institute and Pediatric Rheumatology, Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
⁵ Division of Rheumatology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
⁶ Translational Autoinflammatory Disease Studies Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA.
⁷ Department of Emergency Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
⁸ Center for Critical Care Nephrology, Department of Critical Care Medicine, University of Pittsburgh, School of Medicine, 3550 Terrace Street, 6th floor Scaife Hall, Pittsburgh, PA, 15261, USA.

^# Contributed equally.

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.

Keywords: Ferritin; IL-18; Organ dysfunction; Phenotype; Sepsis.

Abstract

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