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Traumatic brain injury (TBI)-related coagulopathy appears to be most prevalent in patients with tissue hypoperfusion, but evidence for this association is scarce. This study investigated the relationship between tissue perfusion and hemostatic derangements in TBI patients.Coagulation parameters were measured on emergency department admission in patients with TBI (head abbreviated injury scale ≥ 3). The level of hypoperfusion was simultaneously assessed by near-infrared spectroscopy (NIRS) at the forehead and arm, and by base excess and lactate. Coagulopathy was defined as an international normalized ratio1.2 and/or activated partial thromboplastin time40 s and/or thrombocytopenia (120 × 10(9)/L).TBI patients with coagulopathy (42%) had more signs of tissue hypoperfusion as indicated by increased lactate levels (2.1 [1.1-3.2] mmol/L versus 1.2 [1.0-1.7] mmol/L; P = 0.017) and a larger base deficit (-3.0 [-4.6 to -2.0] mmol/L versus -0.1 [-2.5 to 1.8] mmol/L; P 0.001). There was no difference in the cerebral or somatic tissue oxygenation index. However, there was a distinct trend toward a moderate inverse association between the cerebral tissue oxygenation index and D-dimer levels (r=-0.40; P = 0.051) as marker of fibrinolysis. The presence of coagulopathy was associated with an increased inhospital mortality rate (45.5% versus 6.7%; P = 0.002).This is the first study to investigate the relationship between hemostatic derangements and tissue oxygenation using NIRS in TBI patients. This study showed that TBI-related coagulopathy is more profound in patients with metabolic acidosis and increased lactate levels. Although there was no direct relationship between tissue oxygenation and coagulopathy, we observed an inverse relationship between NIRS tissue oxygenation levels and fibrinolysis.

Therapeutic hypothermia (hypo) and valproic acid (VPA, a histone deacetylase inhibitor) have independently been shown to be protective in models of trauma and hemorrhagic shock but require logistically challenging doses to be effective. Theoretically, combined treatment may further enhance effectiveness, allowing us to use lower doses of each modality. The aim of this study was to determine whether a combination of mild hypo and VPA treatments would offer better cytoprotection compared with that of individual treatments in a hemorrhage model.Male Sprague-Dawley rats were subjected to 40% volume-controlled hemorrhage, kept in shock for 30 min, and assigned to one of the following treatment groups: normothermia (36°C-37°C), hypo (30 ± 2°C), normothermia + VPA (300 mg/kg), and hypo + VPA (n = 5 per group). After 3 h of observation, the animals were sacrificed, liver tissue was harvested and subjected to whole cell lysis, and levels of key proteins in the prosurvival Akt pathway were measured using Western blot.Activation of the proapoptotic protein cleaved caspase-3 was significantly lower in the combined treatment group relative to normothermia (P0.05). Levels of the prosurvival Bcl-2 was significantly higher in the combined treatment group relative to sham, normothermia, and normothermia + VPA groups (P0.005). The downstream prosurvival protein phospho-GSK-3β was significantly higher in the sham, hypo, and combined treatment groups compared with that in normothermia groups with or without VPA (P0.05). Levels of the prosurvival β-catenin were significantly higher in the combined treatment group relative to normothermia (P0.01).This is the first in vivo study to demonstrate that combined treatment with VPA and hypo offers better cytoprotection than these treatments given independently.