Exploring ethical conflicts in emergency trauma research: The COMBAT (Control of Major Bleeding after Trauma) study experience

Chin, Theresa L.; Moore, Ernest E.; Coors, Marilyn E.; Chandler, James G.; Ghasabyan, Arsen; Harr, Jeffrey N.; Stringham, James C.; Ramos, Christopher; Ammons, Sarah; Banerjee, Anirban; Sauaia, Angela

doi:10.1016/j.surg.2014.05.021

Cited by 23 publications

(25 citation statements)

References 42 publications

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“…To some extent, it should not be surprising that injury primes the systemic circulation for coagulation, but it is counterintuitive that these clots would be prone to degradation. This finding is supported by previous studies suggesting that postinjury changes in thrombin generation and fibrinolysis are not necessarily linked [28,29]. The separation between tissue injury and hemorrhagic shock in animal models may provide a partial mechanism.…”

Section: Discussionsupporting

confidence: 85%

Viscoelastic measurements of platelet function, not fibrinogen function, predicts sensitivity to tissue‐type plasminogen activator in trauma patients

Moore

Chapman

et al. 2015

Journal of Thrombosis and Haemostasis

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Summary Background Systemic hyperfibrinolysis is a lethal phenotype of trauma-induced coagulopathy. Its pathogenesis is poorly understood. Recent studies have support a central role of platelets in hemostasis and in fibrinolysis regulation, implying that platelet impairment is integral to the development of postinjury systemic hyperfibrinolysis. Objective The objective of this study was to identify if platelet function is associated with blood clot sensitivity to fibrinolysis. We hypothesize that platelet impairment of the ADP pathway correlates with fibrinolysis sensitivity in trauma patients. Methods A prospective observational study of patients meeting the criteria for the highest level of activation at an urban trauma center was performed. Viscoelastic parameters associated with platelet function (maximum amplitude [MA]) were measured with native thrombelastography (TEG), and TEG platelet mapping of the ADP pathway (ADP-MA). The contribution of fibrinogen to clotting was measured with TEG (angle) and the TEG functional fibrinogen (FF) assay (FF-MA). Another TEG assay containing tissue-type plasminogen activator (t-PA) (75 ng mL−1) was used to assess clot sensitivity to an exogenous fibrinolytic stimulus by use of the TEG lysis at 30 min (LY30) variable. Multivariate linear regression was used to identify which TEG variable correlated with t-PA-LY30 (quantification of fibrinolysis sensitivity). Results Fifty-eight trauma patients were included in the analysis, with a median injury severity score of 17 and a base deficit of 6 mEq L−1. TEG parameters that significantly predicted t-PA-LY30 were related to platelet function (ADP-MA, P = 0.001; MA, P < 0.001) but not to fibrinogen (FF-MA, P = 0.773; angle, P = 0.083). Clinical predictors of platelet ADP impairment included calcium level (P = 0.001), base deficit (P = 0.001), and injury severity (P = 0.001). Results and Conclusions Platelet impairment of the ADP pathway is associated with increased sensitivity to t-PA. ADP pathway inhibition in platelets may be an early step in the pathogenesis of systemic hyperfibrinolysis.

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Section: Discussionsupporting

confidence: 85%

Viscoelastic measurements of platelet function, not fibrinogen function, predicts sensitivity to tissue‐type plasminogen activator in trauma patients

Moore

Chapman

et al. 2015

Journal of Thrombosis and Haemostasis

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“…The study was done according to FDA Investigational New Drug regulations (application 15216) and monitored by the Department of Defense Human Research Protection Office. The community consultation and public disclosure processes have been described previously, 19 and the full protocol for the study is available upon request. Patients or next of kin were informed about enrolment at the earliest opportunity and could discontinue participation at any time.…”

Section: Methodsmentioning

confidence: 99%

Plasma-first resuscitation to treat haemorrhagic shock during emergency ground transportation in an urban area: a randomised trial

et al. 2018

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Summary Background Plasma is integral to haemostatic resuscitation after injury, but the timing of administration remains controversial. Anticipating approval of lyophilised plasma by the US Food and Drug Administration, the US Department of Defense funded trials of prehospital plasma resuscitation. We investigated use of prehospital plasma during rapid ground rescue of patients with haemorrhagic shock before arrival at an urban level 1 trauma centre. Methods The Control of Major Bleeding After Trauma Trial was a pragmatic, randomised, single-centre trial done at the Denver Health Medical Center (DHMC), which houses the paramedic division for Denver city. Consecutive trauma patients in haemorrhagic shock (defined as systolic blood pressure [SBP] ≤70 mm Hg or 71–90 mm Hg plus heart rate ≥108 beats per min) were assessed for eligibility at the scene of the injury by trained paramedics. Eligible patients were randomly assigned to receive plasma or normal saline (control). Randomisation was achieved by preloading all ambulances with sealed coolers at the start of each shift. Coolers were randomly assigned to groups 1:1 in blocks of 20 according to a schedule generated by the research coordinators. If the coolers contained two units of frozen plasma, they were defrosted in the ambulance and the infusion started. If the coolers contained a dummy load of frozen water, this indicated allocation to the control group and saline was infused. The primary endpoint was mortality within 28 days of injury. Analyses were done in the as-treated population and by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01838863. Findings From April 1, 2014, to March 31, 2017, paramedics randomly assigned 144 patients to study groups. The as-treated analysis included 125 eligible patients, 65 received plasma and 60 received saline. Median age was 33 years (IQR 25–47) and median New Injury Severity Score was 27 (10–38). 70 (56%) patients required blood transfusions within 6 h of injury. The groups were similar at baseline and had similar transport times (plasma group median 19 min [IQR 16–23] vs control 16 min [14–22]). The groups did not differ in mortality at 28 days (15% in the plasma group vs 10% in the control group, p=0∙37). In the intention-to-treat analysis, we saw no significant differences between the groups in safety outcomes and adverse events. Due to the consistent lack of differences in the analyses, the study was stopped for futility after 144 of 150 planned enrolments. Interpretation During rapid ground rescue to an urban level 1 trauma centre, use of prehospital plasma was not associated with survival benefit. Blood products might be beneficial in settings with longer transport times, but the financial burden would not be justified in an urban environment with short distances to mature trauma centres.

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“…In some settings, ambulance services already carry blood products . The efficacy of giving trauma patients fresh frozen plasma during ambulance transport is currently being investigated in the Control of Major Bleeding After Trauma (COMBAT) Study . Expanding similar capabilities, and linking them to activation of existing massive transfusion protocols at receiving hospitals may improve outcomes in this group.…”

Section: Discussionmentioning

confidence: 99%

Major haemorrhage fatalities in the Australian national coronial database

Gipson

Wood

Cole‐Sinclair

et al. 2017

Emerg Medicine Australasia

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Major bleeding fatalities occurred across a diverse range of contexts, with trauma and gastrointestinal bleeding accounting for most deaths. The majority of patients did not survive to reach hospital. Major haemorrhage occurring entirely outside hospital may be underrecognised from analyses of datasets based primarily on traumatic or in-hospital bleeding. These findings have implications for management of pre-hospital resuscitation and development of clinical practice guidelines for identification and management of major bleeding in the community.

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Exploring ethical conflicts in emergency trauma research: The COMBAT (Control of Major Bleeding after Trauma) study experience

Cited by 23 publications

References 42 publications

Viscoelastic measurements of platelet function, not fibrinogen function, predicts sensitivity to tissue‐type plasminogen activator in trauma patients

Viscoelastic measurements of platelet function, not fibrinogen function, predicts sensitivity to tissue‐type plasminogen activator in trauma patients

Plasma-first resuscitation to treat haemorrhagic shock during emergency ground transportation in an urban area: a randomised trial

Major haemorrhage fatalities in the Australian national coronial database

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