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

Marjolein Heeres,Leo Koenderman,Paul Fw Strengers,Luke Ph Leenen,Karlijn Jp Van Wessem,Tjaakje Visser,Anky Hl Koenderman

doi:10.1186/1745-6215-12-223

Abstract

BackgroundSystemic 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.ObjectiveAttenuation of the surgery-induced additional systemic inflammatory response by perioperative treatment with C1-esterase inhibitor of trauma patients with a femur fracture.MethodsThe 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.ConclusionThis 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.Trial registrationclinicaltrials.gov NCT01275976 (January 12th 2011)

Highlights

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
Trauma patients with a femur fracture, Injury Severity Score ≥ 18 and age 18-80 years are included after obtaining informed consent
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

Summary

Introduction

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, and 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. The lung is most often the first organ to be affected by an exaggerated systemic immune response, which can result in an acute respiratory distress syndrome (ARDS) This functional impairment can be followed by other organs, such as the liver, gastrointestinal tract and kidneys, leading to the so-called multiple organ dysfunction syndrome (MODS). Presence of ARDS and MODS is a major risk factor for mortality, long time morbidity, a prolonged hospital stay and high health care costs [4]

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