Peter Bentzer1,2,3,4, Chris Fjell5,6, Keith R Walley5,6, John Boyd5,6, James A Russell5,6. 1. Centre for Heart Lung Innovation (HLI), University of British Columbia, Vancouver, Canada. peter.bentzer@med.lu.se. 2. Division of Critical Care Medicine, St. Paul's Hospital, University of British Columbia, 1081 Burrard Street, Vancouver, BC, V6Z 1Y6, Canada. peter.bentzer@med.lu.se. 3. Department of Anesthesia and Intensive Care, Helsingborg Hospital, Helsingborg and Lund University, Lund, Sweden. peter.bentzer@med.lu.se. 4. Department of Anesthesiology and Intensive Care, Helsingborg Hospital, 251 87, Helsingborg, Sweden. peter.bentzer@med.lu.se. 5. Centre for Heart Lung Innovation (HLI), University of British Columbia, Vancouver, Canada. 6. Division of Critical Care Medicine, St. Paul's Hospital, University of British Columbia, 1081 Burrard Street, Vancouver, BC, V6Z 1Y6, Canada.
Abstract
PURPOSE: To investigate if plasma cytokine concentrations predict a beneficial response to corticosteroid treatment in septic shock patients. METHODS: A cohort of septic shock patients in whom a panel of 39 cytokines had been measured at baseline (n = 363) was included. Patients who received corticosteroids were propensity score matched to non-corticosteroid-treated patients. An optimal threshold to identify responders to corticosteroid treatment for each cytokine was defined as the concentration above which the odds ratio for 28-day survival between corticosteroid- and non-corticosteroid-treated patients was highest. RESULTS: Propensity score matching partitioned 165 patients into 61 sets; each set contained matched corticosteroid- and non-corticosteroid-treated patients. For 13 plasma cytokines threshold concentrations were found where the odds ratio for survival between corticosteroid- and non-corticosteroid-treated patients was significant (P < 0.05). CD40 ligand was associated with the highest odds ratio and identified 21 % of the patients in the propensity score matched cohort as responders to corticosteroid treatment. Combinations of triplets of cytokines with a significant odds ratio, using the thresholds identified above, were tested to find a higher proportion of responders. IL3, IL6, and CCL4 identified 50 % of the patients in the propensity score matched cohort as responders to corticosteroid treatment. The odds ratio for 28-day survival was 19 (95 % CI 3.5-140, P = 0.02) with a concentration above threshold for a least one of these cytokines. CONCLUSION: Plasma concentration of selected cytokines is a potential predictive biomarker to identify septic shock patients that may benefit from treatment with corticosteroids.
RCT Entities:
PURPOSE: To investigate if plasma cytokine concentrations predict a beneficial response to corticosteroid treatment in septic shockpatients. METHODS: A cohort of septic shockpatients in whom a panel of 39 cytokines had been measured at baseline (n = 363) was included. Patients who received corticosteroids were propensity score matched to non-corticosteroid-treated patients. An optimal threshold to identify responders to corticosteroid treatment for each cytokine was defined as the concentration above which the odds ratio for 28-day survival between corticosteroid- and non-corticosteroid-treated patients was highest. RESULTS: Propensity score matching partitioned 165 patients into 61 sets; each set contained matched corticosteroid- and non-corticosteroid-treated patients. For 13 plasma cytokines threshold concentrations were found where the odds ratio for survival between corticosteroid- and non-corticosteroid-treated patients was significant (P < 0.05). CD40 ligand was associated with the highest odds ratio and identified 21 % of the patients in the propensity score matched cohort as responders to corticosteroid treatment. Combinations of triplets of cytokines with a significant odds ratio, using the thresholds identified above, were tested to find a higher proportion of responders. IL3, IL6, and CCL4 identified 50 % of the patients in the propensity score matched cohort as responders to corticosteroid treatment. The odds ratio for 28-day survival was 19 (95 % CI 3.5-140, P = 0.02) with a concentration above threshold for a least one of these cytokines. CONCLUSION: Plasma concentration of selected cytokines is a potential predictive biomarker to identify septic shockpatients that may benefit from treatment with corticosteroids.
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