D. Liu1, R. A. Namas1, Q. Mi1, O. Abdul-Malak1, J. Guardado1, B. Zuckerbraun1, J. Sperry1, M. Rosengart1, Y. Vodovotz1, B. Timothy1 1University Of Pittsburgh,General Surgery,Pittsburgh, PA, USA
Introduction: Multiple organ dysfunction syndrome (MODS) typically peaks within 5 days of injury and is associated with a complicated clinical course. However, the number of distinct organ failure patterns following injury in humans is unknown. Using MODScore parameter optimized to correlate with adverse in-hospital outcomes, we sought to establish the number of distinct pattern-specific patient clusters present in a highly characterized cohort of blunt trauma patients admitted to the ICU. Inflammatory networks based on measurements of 31 circulating inflammation biomarkers were characterized.
Methods: 376 patients admitted to the ICU and with sequential Marshall MODScores from days (D) 2-5 post-injury were studied. MODScores from D2-D5 were subjected to Fuzzy Clustering Analysis (FCA) to suggest trauma patient sub-groups. Eight widely accepted internal quality indices were calculated to determine the optimal number of trauma patient sub-groups using R. Inflammation biomarkers (31 cytokines and chemokines) were assayed (by Luminex™) in serial blood samples (3 samples within the first 24 h and then daily up to day 5 post-injury). Biomarkers were analyzed using Two-Way ANOVA (p<0.05). Dynamic network analysis (DyNA) was used to suggest dynamic connectivity and complexity among the inflammatory mediators.
Results: Six (75%) of the eight indices suggested that the optimal number of clusters was 4: Group 1 (n=199, age=49 ± 1, male/female [M/F]=134/65, average MODScore=0.3); Group 2 (n=99, age=48 ± 2, M/F=70/29, average MODScore=2); Group 3 (n=53, age=47 ± 3, M/F=36/17, average MODScore=4); and Group 4 (n=25, age=46 ± 4, M/F=20/5, average MODScore=7). There were statistically significant differences among the four groups with regards to ICU LOS, total LOS, and days on mechanical ventilation being all greatest in Group 4, which in turn exhibited a higher incidence of nosocomial infection (76%) when compared to Groups 1, 2, and 3 (16%, 41%, and 49% respectively). Of the 31 circulating biomarkers measured, IL-6, MCP-1, IL-10, IL-8, IP-10, sST2, and MIG were differentially elevated upon presentation and over time among the groups. DyNA suggested a higher sustained degree of systemic interconnectivity in Group 4, which persisted up to D5 post-injury when compared to the other groups.
Conclusion: These results suggest that blunt trauma leads to 4 distinct organ failure patterns in patients who are admitted to the ICU and survive to discharge. The organ failure patterns are preceded by distinct patterns of inflammation biomarkers and followed by severity-specific differences in patients’ in-hospital outcomes.