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

An increase in CD62Ldim neutrophils precedes the development of pulmonary embolisms in COVID-19 patients

OBJECTIVES: A high incidence of pulmonary embolism (PE) is reported in patients with critical Corona Virus Disease 2019 (COVID-19). Neutrophils may contribute to this through a process referred to as immunothrombosis. The aim of this study was to investigate the occurrence of neutrophil subpopulations in blood preceding the development of COVID-19 associated PE. METHODS: We studied COVID-19 patients admitted to the ICU of our tertiary hospital between 19-03-2020 and 17-05-2020. Point-of-care fully automated flow cytometry was performed prior to ICU admission, measuring the neutrophil activation/maturation markers CD10, CD11b, CD16 and CD62L. Neutrophil receptor expression was compared between patients who did or did not develop PE (as diagnosed on CT angiography) during or after their ICU stay. RESULTS: Among 25 eligible ICU patients, 22 subjects were included for analysis, of whom nine developed PE. The median (IQR) time between neutrophil phenotyping and PE occurrence was 9 (7-12) days. A significant increase in the immune-suppressive neutrophil phenotype CD16bright /CD62Ldim was observed on the day of ICU admission (p=0.014) in patients developing PE compared to patients who did not. CONCLUSION: The increase in this neutrophil phenotype indicates that the increased number of CD16bright /CD62Ldim neutrophils might be used as prognostic marker to predict those patients that will develop PE in critical COVID19 patients

Incidence and nature of lower-limb deep vein thrombosis in patients with polytrauma on thromboprophylaxis: A prospective cohort study

Purpose: Deep vein thrombosis (DVT) is common among the severely injured and may lead to pulmonary embolism (PE), which can be life threatening. Thromboprophylaxis may reduce the incidence of venous thromboembolism (VTE); it does not guarantee complete protection. This study’s primary aim was to determine the incidence and nature of lower-limb DVT in polytrauma patients taking prophylaxis. The secondary objective was to assess the incidence of DVT-related complications, including the development of PE and death. Patients and Methods: This prospective observational study included patients age 18 years or older who presented with polytrauma directly from the scene and were admitted into the trauma unit between March 1, 2020 and August 31, 2020. All patients underwent lower-limb ultrasound during their hospital course to diagnose DVT. Results: A total of 169 patients underwent extremity Doppler ultrasound to detect DVT. Of these, 69 patients (40.8%) were considered at the highest-risk for VTE development. For VTE prophylaxis, 115 patients (68%) received pharmacologic agents, and 54 patients (32%) had intermittent pneumatic compression on admission. Three patients (1.8%) developed DVT despite prophylaxis. Four patients (2.4%) developed PE during the index presentation and were diagnosed between days 3 and 13 after injury. Early DVT was not detected in any patients with diagnosed PE. Overall, nine patients (5.33%) died, but no in-hospital deaths were related to DVT and/or PE. Conclusion: The incidence of DVT in polytrauma patients remains low in our small series, perhaps because of the mandatory VTE risk assessment for all hospitalized patients and the early initiation of prophylaxis. Using a trauma center registry to measure DVT and PE incidence regularly is recommended to improve trauma care quality

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