• Jack O Zhao, Bhakti K Patel, Paulette Krishack, Matthew R Stutz, Steven D Pearson, Julie Lin, Paola A Lecompte-Osorio, Karen C Dugan, Seoyoen Kim, Nicole Gras, Anne Pohlman, John P Kress, Jesse B Hall, Anne I Sperling, Ayodeji Adegunsoye, Philip A Verhoef, and Krysta S Wolfe.
• Pulmonary and Critical Care, University of Chicago Medical Center, Chicago, IL.
• Crit. Care Med. 2023 Dec 1; 51 (12): e253e263e253-e263.

ObjectivesTo identify cytokine signature clusters in patients with septic shock.DesignProspective observational cohort study.SettingSingle academic center in the United States.PatientsAdult (≥ 18 yr old) patients admitted to the medical ICU with septic shock requiring vasoactive medication support.InterventionsNone.Measurements And Main ResultsOne hundred fourteen patients with septic shock completed cytokine measurement at time of enrollment (t 1 ) and 24 hours later (t 2 ). Unsupervised random forest analysis of the change in cytokines over time, defined as delta (t 2 -t 1 ), identified three clusters with distinct cytokine profiles. Patients in cluster 1 had the lowest initial levels of circulating cytokines that decreased over time. Patients in cluster 2 and cluster 3 had higher initial levels that decreased over time in cluster 2 and increased in cluster 3. Patients in clusters 2 and 3 had higher mortality compared with cluster 1 (clusters 1-3: 11% vs 31%; odds ratio [OR], 3.56 [1.10-14.23] vs 54% OR, 9.23 [2.89-37.22]). Cluster 3 was independently associated with in-hospital mortality (hazard ratio, 5.24; p = 0.005) in multivariable analysis. There were no significant differences in initial clinical severity scoring or steroid use between the clusters. Analysis of either t 1 or t 2 cytokine measurements alone or in combination did not reveal clusters with clear clinical significance.ConclusionsLongitudinal measurement of cytokine profiles at initiation of vasoactive medications and 24 hours later revealed three distinct cytokine signature clusters that correlated with clinical outcomes.Copyright © 2023 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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