Elevated Admission Base Deficit Is Associated with a Complex Dynamic Network of Systemic Inflammation Which Drives Clinical Trajectories in Blunt Trauma Patients

Abstract

We hypothesized that elevated base deficit (BD) ≥ 4 mEq/L upon admission could be associated with an altered inflammatory response, which in turn may impact differential clinical trajectories. Using clinical and biobank data from 472 blunt trauma survivors, 154 patients were identified after excluding patients who received prehospital IV fluids or had alcohol intoxication. From this subcohort, 84 patients had a BD ≥ 4 mEq/L and 70 patients with BD < 4 mEq/L. Three samples within the first 24 h were obtained from all patients and then daily up to day 7 after injury. Twenty-two cytokines and chemokines were assayed using Luminex™ and were analyzed using two-way ANOVA and dynamic network analysis (DyNA). Multiple mediators of the innate and lymphoid immune responses in the BD ≥ 4 group were elevated differentially upon admission and up to 16 h after injury. DyNA revealed a higher, sustained degree of interconnectivity of the inflammatory response in the BD ≥ 4 patients during the initial 16 h after injury. These results suggest that elevated admission BD is associated with differential immune/inflammatory pathways, which subsequently could predispose patients to follow a complicated clinical course.

Figure 1

(a) Arterial base deficit (BD) from time of admission up to 7 days after injury between BD ≥ 4 and BD < 4 subgroups. The BD ≥ 4 group had statistically significantly elevated BD levels at 8 h and 16 h after injury when compared to the BD < 4 group. BD in both subgroups approach similar values at 24 h after injury. ^∗ P < 0.05 by two-way ANOVA. (b) Plasma lactate levels from time of admission up to 7 days after injury between BD ≥ 4 and BD < 4 subgroups. The BD ≥ 4 group had statistically significantly elevated lactate levels at 8 h after injury when compared to the BD < 4 group. BD in both subgroups approaches normal values at 24 h after injury. ^∗ P < 0.05 by two-way ANOVA.

Figure 2

(a) Differences in (a) admission systolic blood pressure (SBP), (b) admission heart rate (HR), and (c) Shock Index between BD ≥ 4 and BD < 4 subgroups. (a) Admission SBP, (b) admission HR, and (c) Shock Index (HR/SBP) were statistically significantly different in the BD ≥ 4 group when compared to the BD < 4 group. ^∗ P < 0.05 by Mann–Whitney U test.

Figure 3

(a) Abbreviated injury scale (AIS) analysis of injury patterns in BD ≥ 4 and BD < 4 subgroups. The BD ≥ 4 group exhibited greater extremity injury when compared to the BD < 4 group. ^∗ P < 0.05 by Mann–Whitney U test. (b) Multiple Organ Dysfunction Score (MODScore) in BD ≥ 4 and BD < 4 subgroups from days 1 through 7 after injury. The BD ≥ 4 group had a statistically significantly higher degree of organ dysfunction from days 2 to 4 after injury compared to the BD < 4 group. ^∗ P < 0.05 by two-way ANOVA.

Figure 4

(a) Percentage of patients requiring urgent surgical interventions upon discharge from the trauma bay. 61% of patients in the BD ≥ 4 group required immediate surgical interventions compared to 41% in the BD < 4 group. ^∗ P < 0.05 by Chi-square. (b) Relative risk of requiring operative management in the first 24 h after trauma. Having an admission BD ≥ 4 is associated with a 1.5-fold risk of requiring surgical interventions in the first 24 h after injury. ^∗RR = 1.5; 95% CI [1.056–2.033]; P < 0.05.

Figure 5

Dynamic network analysis (DyNA) of inflammatory mediators in BD ≥ 4 and BD < 4 subgroups suggests an early differential network connectivity within 16 h after injury. DyNA at 0–8 h suggested that IFN-α/sIL-2Rα/MIP-1α/IL-17A/IL-4/GM-CSF/IL-7/IL-2/IFN-γ/IL-13 were highly connected in the BD ≥ 4 group (a) while the BD < 4 group (d) exhibited a lesser degree of connected nodes: MIP-1α/sIL-2Rα/MIP-1β/IL-4/IL-1β/IL-2/IL-15. DyNA at 8–16 h suggested that the BD ≥ 4 group (b) retained the connectivity among inflammatory mediators, whereas the BD < 4 group (e) continued to exhibit a lesser degree of connections. DyNA at 16–24 h suggested that the BD ≥ 4 group (c) exhibited a substantial reduction of network connectivity to a level similar to BD < 4 group (f).

Figure 6

(a) Network complexity differs between the BD ≥ 4 and BD < 4 subgroups over the first 24 h after injury. The BD ≥ 4 group exhibited a higher network density at 8 h and 16 h after injury which progressively decreased to similar levels of BD < 4 group at 24 h after injury. (b) Arterial BD levels within 24 h after injury. BD levels in both BD ≥ 4 and BD < 4 subgroups mirror the density of their corresponding inflammatory networks.