Fibrinogen supplementation for the trauma patient: Should you choose fibrinogen concentrate over cryoprecipitate?

BACKGROUND: Trauma-induced coagulopathy is frequently associated with hypofibrinogenemia. Cryoprecipitate (Cryo), and fibrinogen concentrate (FC) are both potential means of fibrinogen supplementation. The aim of this study was to compare the outcomes of traumatic hemorrhagic patients who received fibrinogen supplementation using FC versus Cryo. METHODS: We performed a 2-year (2016-2017) retrospective cohort analysis of the American College of Surgeons Trauma Quality Improvement Program database. All adult trauma patients (≥18 years) who received FC or Cryo as an adjunct to resuscitation were included. Patients with bleeding disorders, chronic liver disease, and those on preinjury anticoagulants were excluded. Patients were stratified into those who received FC, and those who received Cryo. Propensity score matching (1:2) was performed. Outcome measures were transfusion requirements, major complications, hospital, and intensive care unit lengths of stay, and mortality. RESULTS: A matched cohort of 255 patients who received fibrinogen supplementation (85 in FC, 170 in Cryo) was analyzed. Overall, the mean age was 41 ± 19 years, 74% were male, 74% were white and median Injury Severity Score was 26 (22-30). Compared with the Cryo group, the FC group required less units of packed red blood cells, fresh frozen plasma, and platelets, and had shorter in-hospital and intensive care unit length of stay. There were no significant differences between the two groups in terms of major in-hospital complications and mortality. CONCLUSION: Fibrinogen supplementation in the form of FC for the traumatic hemorrhagic patient is associated with improved outcomes and reduced transfusion requirements as compared with Cryo. Further studies are required to evaluate the optimal method of fibrinogen supplementation in the resuscitation of trauma patients. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Glutamine attenuation of cell death and inducible nitric oxide synthase expression following inflammatory cytokine-induced injury is dependent on heat shock factor-1 expression.

BACKGROUND: Glutamine (GLN) has been shown to improve outcome after experimental and clinical models of critical illness. Enhanced expression of heat shock protein (HSP) has been hypothesized to be responsible for this protection. The heat shock response has been shown to inhibit inducible nitric oxide synthase (iNOS) gene expression and nitric oxide (NO) production. This study tested the hypothesis that GLN-mediated activation of the HSP pathway is responsible for improved survival and attenuation of iNOS expression after an inflammatory cytokine-induced injury. METHODS: Heat shock factor-1 (HSF-1) wild-type and knockout mouse embryonic fibroblasts (HSF-1+/+ and HSF-1-/-) were used in all experiments. Cells were treated with 0 mmol/L or 8 mmol/L GLN and cytomix (tumor necrosis factor-alpha, lipopolysaccharide, and interferon-gamma) in a concurrent treatment model once they had reached confluence. Cell viability was assayed with MTS/PMS mixture. Apoptosis and necrosis were assayed via immunohistochemistry. iNOS and HSP-70 expression were detected via Western blotting. NO production was measured using the Griess reagent. RESULTS: GLN treatment significantly attenuated inflammatory cytokine-induced cell death and apoptosis in HSF-1+/+ cells vs 0 mmol/L GLN treatment; however, GLN's cellular protection was lost in HSF-1-/- cells. GLN supplementation attenuated cytomix-induced iNOS expression and NO production only in HSF-1+/+ cells. Further, GLN induced HSP-70 expression only in HSF-1+/+ cells. CONCLUSIONS: This is the first demonstration that GLN-mediated cellular protection after inflammatory cytokine injury is due to HSF-1 expression and cellular capacity to activate an HSP response.