The effect of C1-esterase inhibitor on systemic inflammation in trauma patients with a femur fracture - The CAESAR study: study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Systemic inflammation in response to a femur fracture and the additional fixation is associated with inflammatory complications, such as acute respiratory distress syndrome and multiple organ dysfunction syndrome. The injury itself, but also the additional procedure of femoral fixation induces a release of pro-inflammatory cytokines such as interleukin-6. This results in an aggravation of the initial systemic inflammatory response, and can cause an increased risk for the development of inflammatory complications. Recent studies have shown that administration of the serum protein C1-esterase inhibitor can significantly reduce the release of circulating pro-inflammatory cytokines in response to acute systemic inflammation.</p> <p>Objective</p> <p>Attenuation of the surgery-induced additional systemic inflammatory response by perioperative treatment with C1-esterase inhibitor of trauma patients with a femur fracture.</p> <p>Methods</p> <p>The study is designed as a double-blind randomized placebo-controlled trial. Trauma patients with a femur fracture, Injury Severity Score ≥ 18 and age 18-80 years are included after obtaining informed consent. They are randomized for administration of 200 U/kg C1-esterase inhibitor intravenously or placebo (saline 0.9%) just before the start of the procedure of femoral fixation. The primary endpoint of the study is Δ interleukin-6, measured at t = 0, just before start of the femur fixation surgery and administration of C1-esterase inhibitor, and t = 6, 6 hours after administration of C1-esterase inhibitor and the femur fixation.</p> <p>Conclusion</p> <p>This study intents to identify C1-esterase inhibitor as a safe and potent anti-inflammatory agent, that is capable of suppressing systemic inflammation in trauma patients. This might facilitate early total care procedures by lowering the risk of inflammation in response to the surgical intervention. This could result in increased functional outcomes and reduced health care related costs.</p> <p>Trial registration</p> <p>clinicaltrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT01275976">NCT01275976</a> (January 12th 2011)</p

Intensive care organisation: Should there be a separate intensive care unit for critically injured patients?

In the last two decennia, the mixed population general intensive care unit (ICU) with a “closed format” setting has gained in favour compared to the specialized critical care units with an “open format” setting. However, there are still questions whether surgical patients benefit from a general mixed ICU. Trauma is a significant cause of morbidity and mortality throughout the world. Major or severe trauma requiring immediate surgical intervention and/or intensive care treatment. The role and type of the ICU has received very little attention in the literature when analyzing outcomes from critical injuries. Severely injured patients require the years of experience in complex trauma care that only a surgery/trauma ICU can provide. Should a trauma center have the capability of a separate specialized ICU for trauma patients (“closed format”) next to its standard general mixed IC

Impaired bone healing in multitrauma patients is associated with altered leukocyte kinetics after major trauma

Animal studies have shown that the systemic inflammatory response to major injury impairs bone regeneration. It remains unclear whether the systemic immune response contributes to impairment of fracture healing in multitrauma patients. It is well known that systemic inflammatory changes after major trauma affect leukocyte kinetics. We therefore retrospectively compared the cellular composition of peripheral blood during the first 2 weeks after injury between multitrauma patients with normal (n=48) and impaired (n=32) fracture healing of the tibia. The peripheral blood-count curves of leukocytes, neutrophils, monocytes, and thrombocytes differed significantly between patients with normal and impaired fracture healing during the first 2 weeks after trauma (P-values were 0.0122, 0.0083, 0.0204, and <0.0001, respectively). Mean myeloid cell counts were above reference values during the second week after injury. Our data indicate that leukocyte kinetics differ significantly between patients with normal and impaired fracture healing during the first 2 weeks after major injury. This finding suggests that the systemic immune response to major trauma can disturb tissue regeneration

Impaired bone healing in multitrauma patients is associated with altered leukocyte kinetics after major trauma

Animal studies have shown that the systemic inflammatory response to major injury impairs bone regeneration. It remains unclear whether the systemic immune response contributes to impairment of fracture healing in multitrauma patients. It is well known that systemic inflammatory changes after major trauma affect leukocyte kinetics. We therefore retrospectively compared the cellular composition of peripheral blood during the first 2 weeks after injury between multitrauma patients with normal (n=48) and impaired (n=32) fracture healing of the tibia. The peripheral blood-count curves of leukocytes, neutrophils, monocytes, and thrombocytes differed significantly between patients with normal and impaired fracture healing during the first 2 weeks after trauma (P-values were 0.0122, 0.0083, 0.0204, and <0.0001, respectively). Mean myeloid cell counts were above reference values during the second week after injury. Our data indicate that leukocyte kinetics differ significantly between patients with normal and impaired fracture healing during the first 2 weeks after major injury. This finding suggests that the systemic immune response to major trauma can disturb tissue regeneration