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Shock-induced systemic hyperfibrinolysis is attenuated by plasma-first resuscitation.

ABSTRACT: We developed a hemorrhagic shock animal model to replicate an urban prehospital setting where resuscitation fluids are limited to assess the effect of saline versus plasma in coagulopathic patients. An in vitro model of whole blood dilution with saline exacerbated tissue plasminogen activator (tPA)-mediated fibrinolysis, while plasma dilution did not change fibrinolysis. We hypothesize that shock-induced hyperfibrinolysis can be attenuated by resuscitation with plasma while exacerbated by saline.Sprague-Dawley rats were hemorrhaged to a mean arterial pressure of 25 mm Hg and maintained in shock for 30 minutes. Animals were resuscitated with either normal saline (NS) or platelet-free plasma (PFP) with a 10% total blood volume bolus, followed by an additional 5 minutes of resuscitation with NS to increase blood pressure to a mean arterial pressure of 30 mm Hg. Animals were observed for 15 minutes for the assessment of hemodynamic response and survival. Blood samples were analyzed with thrombelastography paired with protein analysis.The median percentage of total blood volume shed per group were similar (NS, 52.5% vs. PFP, 55.7; p = 0.065). Survival was 50% in NS compared with 100% in PFP. The change in LY30 and tPA levels from baseline to shock was similar between groups (LY30 PFP, 10; interquartile range [IQR], 4.3-11.2; NS, 4.5; IQR, 4.1-14.2; p = 1.00; tPA PFP, 16.6 ng/mL; IQR, 13.7-27.8; NS, 22.4; IQR, 20.1-25.5; p = 0.240). After resuscitation, the median change in LY30 was greater in the NS group (13.5; IQR, 3.5-19.9) compared with PFP (-4.9%; IQR, -9.22 to 0.25 p = 0.004), but tPA levels did not significantly change (NS, 1.4; IQR, -6.2 to 7.1 vs. PFP, 1.7; IQR, -5.2 to 6.8; p = 0.699).Systemic hyperfibrinolysis is driven by hypoperfusion and associated with increased levels of tPA. Plasma is a superior resuscitation fluid to NS in a prehospital model of severe hemorrhagic shock as it attenuates hyperfibrinolysis and improves systemic perfusion.

SUBMITTER: Moore HB

PROVIDER: S-EPMC4686159 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Shock-induced systemic hyperfibrinolysis is attenuated by plasma-first resuscitation.

Moore Hunter B HB Moore Ernest E EE Morton Alexander P AP Gonzalez Eduardo E Fragoso Miguel M Chapman Michael P MP Dzieciatkowska Monika M Hansen Kirk C KC Banerjee Anirban A Sauaia Angela A Silliman Christopher C CC

The journal of trauma and acute care surgery 20151201 6

<h4>Background</h4>We developed a hemorrhagic shock animal model to replicate an urban prehospital setting where resuscitation fluids are limited to assess the effect of saline versus plasma in coagulopathic patients. An in vitro model of whole blood dilution with saline exacerbated tissue plasminogen activator (tPA)-mediated fibrinolysis, while plasma dilution did not change fibrinolysis. We hypothesize that shock-induced hyperfibrinolysis can be attenuated by resuscitation with plasma while ex ...[more]

PMID: 26680132

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Project description:BackgroundPlasma 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.MethodsThe 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.FindingsFrom 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.InterpretationDuring 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.FundingUS Department of Defense.

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Shock-induced systemic hyperfibrinolysis is attenuated by plasma-first resuscitation.

Publications

Shock-induced systemic hyperfibrinolysis is attenuated by plasma-first resuscitation.

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