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Identification of Clinically Significant Cytokine Signature Clusters in Patients With Septic Shock
Jack O Zhao1, Bhakti K Patel1, Paulette Krishack1
1Pulmonary and Critical Care, University of Chicago Medical Center, Chicago, IL.
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.
