Identification of Clinically Significant Cytokine Signature Clusters in Patients With Septic Shock.

Objectives: To identify cytokine signature clusters in patients with septic shock.
Design: Prospective observational cohort study.
Setting: Single academic center in the United States.
Patients: Adult (≥ 18 yr old) patients admitted to the medical ICU with septic shock requiring vasoactive medication support.
Interventions: None.
Measurements and Main Results: One 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.
Conclusions: Longitudinal measurement of cytokine profiles at initiation of vasoactive medications and 24 hours later revealed three distinct cytokine signature clusters that correlated with clinical outcomes.
Competing Interests: Drs. Zhao, Patel, Stutz, Pearson, Adegunsoye, and Verhoef received support for article research from the National Institutes of Health (NIH). Dr. Patel’s institution received funding from the NIH (K23 HL148387); she received funding from The American College of Chest Physicians and Merck. Dr. Pearson received funding from the National Heart, Lung, and Blood Institute (NHLBI) (T32 HL 7605). Dr. Hall received funding from McGraw Hill Publishing. Drs. Hall and Adegunsoye received funding from the American College of Chest Physicians. Dr. Adegunsoye received funding from the Pulmonary Fibrosis Foundation and the NIH; he disclosed that he serves on a pulmonary fibrosis educational forum and advisory board for Boehringer Ingelheim, Inogen, and Roche. Dr. Verhoef’s institution received funding from the NHLBI. The remaining authors have disclosed that they do not have any potential conflicts of interest.
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