scholarly journals Mitochondrial dysfunction in trauma-related coagulopathy – Is there causality? – Study protocol for a prospective observational study

2021 ◽  
Author(s):  
Péter Jávor ◽  
Ferenc Rárosi ◽  
Tamara Horváth ◽  
László Török ◽  
Petra Hartmann

Hemorrhage control often poses a great challenge for clinicians due to trauma-induced coagulopathy (TIC). The pathogenesis of TIC is not completely revealed; however, growing evidence attributes a central role to altered platelet biology. The activation of thrombocytes and subsequent clot formation are highly energetic processes being tied to mitochondrial activity, and the inhibition of the electron transport chain (ETC) impedes on thrombogenesis, suggesting the potential role of mitochondria in TIC. Our present study protocol provides a guide to quantitatively characterize the derangements of mitochondrial functions in TIC. One hundred eleven severely injured (Injury Severity Score ≥16), bleeding trauma patients with an age of 18 or greater will be included in this prospective observational study. Patients receiving oral antiplatelet agents including cyclooxygenase-1 or adenosine diphosphate receptor inhibitors (aspirin, clopidogrel, prasugrel, and ticagrelor) will be excluded from the final analysis. Hemorrhage will be confirmed and assessed with computer tomography. Conventional laboratory markers of hemostasis such as prothrombin time and international normalized ratio (INR) will be measured and rotational thromboelastometry (ROTEM) will be performed directly upon patient arrival. Platelets will be isolated from venous blood samples and subjected to high-resolution fluororespirometry (Oxygraph-2k, Oroboros Instruments, Innsbruck, Austria) to evaluate the efficacy of mitochondrial respiration. Oxidative phosphorylation (OxPhos), coupling of the ETC, mitochondrial superoxide formation, mitochondrial membrane potential changes and extramitochondrial Ca2+-movement will be recorded. The association between OxPhos capacity of platelet mitochondria and numerical parameters of ROTEM aggregometry will constitute our primary outcome. The relation between OxPhos capacity and results of viscoelastic assays and conventional markers of hemostasis will serve as secondary outcomes. The association of the OxPhos capacity of platelet mitochondria upon patient arrival to the need for massive blood transfusion (MBT) and 24-hour mortality will constitute our tertiary outcomes. Mitochondrial dysfunction and its importance in TIC in are yet to be assessed for the deeper understanding of this common, life-threatening condition. Disclosure of mitochondria-mediated processes in thrombocytes may reveal new therapeutic targets in the management of hemorrhaging trauma patients, thereby leading to a reduction of potentially preventable mortality. The present protocol was registered to ClinicalTrials.gov on 12 August 2021, under the reference number NCT05004844.

CJEM ◽  
2020 ◽  
Vol 22 (S1) ◽  
pp. S47-S47
Author(s):  
M. Kulas ◽  
L. Brueton-Campbell ◽  
E. Weldon ◽  
N. McDonald ◽  
R. Pryce

Introduction: This was a prospective observational study involving a convenience sample of low-risk trauma patients presenting to a Level 1 Trauma Centre under spinal motion restriction (SMR). To our knowledge no prior studies have objectively measured head-neck (H-N) motion in trauma patients with suspected spine injuries during emergency department (ED) care. The goal was to establish the feasibility of deploying non-invasive motion sensors on trauma patients in the ED and to provide initial estimates for H-N kinematics under SMR during different phases of treatment. Methods: Low-risk adult patients treated by Winnipeg Fire Paramedic Service who sustained non-life threatening trauma with the potential for spine injury were eligible for inclusion. Participants received usual pre-hospital care; application of spine board and/or cervical collar, as determined by local practice protocol. Inertial measurement units (IMUs) were placed on participant's forehead, sternum and stretcher upon arrival to the ED. Data was collected during three phases of care: patient handling (log rolls, transfers, clothing removal); stretcher movement (to imaging, etc); stretcher stationary. IMUs were removed upon disposition decision by the attending physician. IMUs yielded data on H-N motion in terms of linear acceleration (resultant) and angular displacement (rotation + flexion-extension + side-flexion = total). Peak (M +/- SE) displacements and accelerations are reported, with comparisons across treatment phases using repeated measures ANOVA. Results: Eleven patients were enrolled in the study (age: 49 +/- 16 years; Injury Severity Score 13.4 +/- 9.9; female = 2). Substantial H-N motion was observed during ED care. Total H-N displacement (28.6 +/- 3.6 deg) and acceleration (7.8 +/- 1.0 m/s2) were higher during patient handling compared to stretcher moving (13.0 +/- 2.5 deg; 4.6 +/- 0.9 m/s2; p < .05) but not while the stretcher was stationary (18.9 +/- 3.4 deg; 5.4 +/- 1.2 m/s2; p > .06). Similar differences were detected for side-flexion and flexion-extension (p < .05), with peak displacements of 11.4+/-1.5 deg and 14.6 +/- 2.2 deg during patient handling, respectively. Conclusion: IMU use on trauma patients safely described H-N motion kinematics in a small sample of patients with different spectrums of illness during their care in the ED. Future studies utilizing IMUs could inform ED spine motion restriction protocols and compare movement of patients in specific subsets (intoxicated, spinal tenderness, injury severity etc.).


2020 ◽  
pp. 102490792091125
Author(s):  
Chia-Peng Chang ◽  
Cheng-Ting Hsiao ◽  
Cheng-Hsien Wang ◽  
Kai-Hua Chen ◽  
I-Chuan Chen ◽  
...  

Background: Hyperglycemia in the acute phase after trauma is a stress response and a metabolic reflection in humans with injury, which could adversely affect outcome in trauma patients. In this study, we attempted to identify if hyperglycemia a reliable predictor for mortality in major trauma patients. Objectives: In order to identify if hyperglycemia a reliable predictor for mortality in major trauma, we designed and proformed a prospective observational study in a tertiary hospital. Method: We performed a prospective observational study to review the records of 601 patients with major trauma (injury severity scores >15) who visited our hospital’s emergency department from August 2012 to July 2015. Logistic regression was performed to assess the effect of hyperglycemia on mortality. Result: Major trauma patients in the hyperglycemia group had low systolic/diastolic blood pressure at triage, low initial Glasgow Coma Scale score, high incidence of hypotension episodes, coagulopathy, acidosis, and anemia. Hyperglycemia was significantly correlated with mortality in major trauma patients in this study (odds ratio: 1.97, 95% confidence interval: 1.04–3.74). Conclusion: In major trauma patients with injury severity scores >15, hyperglycemia has a positive correlation with mortality, which could be a predictor of mortality in clinical practice.


2020 ◽  
Author(s):  
Islam Elabbassy ◽  
Wafaa M. Hussein ◽  
Maged El-Setouhy ◽  
Jon Mark Hirshon ◽  
Mohamed El-Shinawi

Abstract Background: "Delayed discharge" is defined as patients who remain hospitalized beyond the time of being fit for discharge. There is no standardized amount of time defining delayed discharge documented in the literature, and there is a lack of evidence about this topic in Egypt. This study aims to identify the factors associated with discharge delays.Methods: A prospective observational study included all trauma patients admitted to a University Hospital in Egypt over two months. The time of the decision of discharge and actual discharge time were recorded by reviewing patients' medical records. The patients and their caregivers were asked to fill in a questionnaire about the reasons for delayed discharge. Potential reasons for the delayed discharge were classified into system-related, medical and family-related factors. Results: The study included 498 patients with a median age of 41 years (9 – 72). The median time until the actual discharge was three hours. System-related factors were documented in 48.8% of cases, followed by medical factors (36.3%), and family-related factors (28.1%). When controlling for age, gender and injury severity score using a logistic regression analysis, longer time to discharge (≥ 3 hours) showed a stronger association with medical factors [adjusted OR (95% CI) = 5.44 (2.73-10.85)] and family-related factors [adjusted OR (95% CI) = 7.94 (3.40-18.54)] compared to system-related factors [adjusted OR (95% CI) = 2.20 (1.12-4.29)].Conclusion: Although system-related factors were more prevalent, medical and family-related factors appear to be associated with longer discharge delays compared to system-related factors.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Hironori Matsumoto ◽  
Jun Takeba ◽  
Kensuke Umakoshi ◽  
Satoshi Kikuchi ◽  
Muneaki Ohshita ◽  
...  

Abstract Background We conducted a prospective observational study for investigating the changes in the 13th member of a disintegrin-like and metalloprotease with thrombospondin type 1 motif (ADAMTS13) and its association with the coagulofibrinolytic response in adult trauma patients. Methods In 39 trauma patients hospitalized for longer than 7 days, time-course changes in biomarkers of coagulofibrinolysis and systemic inflammation along with ADAMTS13 activity were examined. The patients were stratified into three groups based on ADAMTS13 activities on admission (day 0): normal group (≥70%), mildly decreased group (≥50 and < 70%) and moderately decreased group (< 50%). Results Among 39 patients with a median Injury Severity Score (ISS) of 20, 11 patients developed disseminated intravascular coagulation (DIC) and 16 patients required transfusion. Six of 39 patients (15.4%) showed moderate decreased ADAMTS13 activity to < 50%, and 20 patients (51.3%) showed mild drops (≥50 and < 70%). These changes in ADAMTS13 activity on day 0 were significantly correlated with changes in IL-6 and other coagulofibrinolytic markers such as platelet counts, prothrombin time and fibrin/fibrinogen degradation product (FDP). Antithrombin activity (AT) and serum albumin (Alb) level showed significantly positive linear correlations with ADAMTS13 activity (AT: r = 0.513, p < 0.001; Alb: r = 0.647, p < 0.001). Simple logistic regression analyses showed that ADAMTS13 activity, if less than 50%, was significantly correlated with the development of DIC (OR 7.499, 95%CI 1.121–49.242, p = 0.038) and the need for transfusion of fresh frozen plasma (OR 9.000, 95%CI 1.327–61.025, p = 0.028). Conclusions ADAMTS13 activity decreased even in the early phase of trauma, which was complicated by coagulopathy and systemic inflammation. Furthermore, the decrease in ADAMTS13 activity was correlated with DIC and plasma transfusion.


2009 ◽  
Vol 36 (S 02) ◽  
Author(s):  
B Hotter ◽  
S Pittl ◽  
M Ebinger ◽  
G Oepen ◽  
K Jegzentis ◽  
...  

BMJ Open ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. e045826
Author(s):  
Arjun Chandna ◽  
Endashaw M Aderie ◽  
Riris Ahmad ◽  
Eggi Arguni ◽  
Elizabeth A Ashley ◽  
...  

IntroductionIn rural and difficult-to-access settings, early and accurate recognition of febrile children at risk of progressing to serious illness could contribute to improved patient outcomes and better resource allocation. This study aims to develop a prognostic clinical prediction tool to assist community healthcare providers identify febrile children who might benefit from referral or admission for facility-based medical care.Methods and analysisThis prospective observational study will recruit at least 4900 paediatric inpatients and outpatients under the age of 5 years presenting with an acute febrile illness to seven hospitals in six countries across Asia. A venous blood sample and nasopharyngeal swab is collected from each participant and detailed clinical data recorded at presentation, and each day for the first 48 hours of admission for inpatients. Multianalyte assays are performed at reference laboratories to measure a panel of host biomarkers, as well as targeted aetiological investigations for common bacterial and viral pathogens. Clinical outcome is ascertained on day 2 and day 28.Presenting syndromes, clinical outcomes and aetiology of acute febrile illness will be described and compared across sites. Following the latest guidance in prediction model building, a prognostic clinical prediction model, combining simple clinical features and measurements of host biomarkers, will be derived and geographically externally validated. The performance of the model will be evaluated in specific presenting clinical syndromes and fever aetiologies.Ethics and disseminationThe study has received approval from all relevant international, national and institutional ethics committees. Written informed consent is provided by the caretaker of all participants. Results will be shared with local and national stakeholders, and disseminated via peer-reviewed open-access journals and scientific meetings.Trial registration numberNCT04285021.


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