Steroid-loaded Hemostatic Nanoparticles Alleviate Injury Progression after Blast Trauma
The purpose of this study was to investigate whether hemostatic dexamethasone-loaded nanoparticles (hDNP) functionalized with a peptide that binds with activated platelets could reduce cellular injury and improve functional outcomes in a model of blast trauma. Functionalized nanoparticles, or synthetic platelets, offer a wide variety of benefits and advantages compared to alternatives, such as increased biocompatibility and targeting of the injury site (DePalma, 2005). Blood loss is the primary cause of death at acute time points post injury in both civilian and battlefield traumas. Currently, there is a shortage in treatments for internal bleeding, especially for rapid administration in open field combat. In a recent U.K. study, less than fifty percent of soldiers diagnosed with primary blast lung injury (PBLI), the most common fatal blast injury, survived to reach a medical facility (Smith, 2011). This study examines potential therapeutic effects of hDNP on subacute recovery in brain pathology and behavior after blast polytrauma. An established polytrauma model that simulates severe injury, including PBLI and blast-induced neurotrauma (BINT), can be used to evaluate life-saving therapeutics (Hubbard, 2014). Poly(lactic-co-glycolic acid)-based nanoparticles with poly(ethylene glycol) arms and the arginine-glycine-aspartic acid (RGD) peptide to target activated platelets were fabricated. A blast-induced polytrauma rodent model was used to evaluate the functionalized nanoparticles at an acute stage. After anesthesia, Male Sprague Dawley rats were exposed to a single, representative “free field” blast wave from an Advanced Blast Simulator at Virginia Tech at a peak overpressure of 28 psi for 2.5 ms duration, operating above 50% lethality risk, in a sidethorax orientation (Hubbard, 2014). After injury, animals were immediately injected intravenously with hDNP, control dexamethasone-loaded nanoparticles (cDNP), or lactated ringers (LR) and physiological parameters were monitored. Sham animals were not injected or exposed to the blast wave. Open field assays were performed on surviving animals to measure levels of anxiety. At one week post-blast, brains were extracted and sections from the amygdala were obtained for immunofluorescent staining using glial fibrillary acidic protein (GFAP; activated astrocytes), cleaved caspase-3 (apoptosis), and SMI-71 (blood-brain barrier). According to physiological monitoring immediately after blast, oxygen saturation was significantly decreased in the control and LR groups compared to the active and sham groups. Using the open field test, elevated anxiety parameters were found in the control and LR groups compared to the hDNP group. GFAP was significantly elevated in the control group compared to the hDNP and sham groups in the amygdala. Caspase-3 was also significantly elevated in the control group compared to the hDNP group. SMI-71 was significantly reduced in the LR group compared to the sham group. hDNP treatment has the potential to assist recovery after internal hemorrhage. Immediate intervention to assuage hemorrhage, one source for injury pathology, is crucial to mitigate debilitating injury mechanisms that lead to cognitive and emotional deficits (Shetty, 2014).
It is possible that through prevention of microhemorrhaging of the blood-brain barrier (BBB), hDNP was able to mitigate cellular injury and improve cognitive outcomes. Future studies will evaluate the effect on inflammatory and hypoxia-related proteins after hDNP administration post-trauma.
Red Blood Cell Transfusion and Mortality in Trauma Patients: Risk-Stratified Analysis of an Observational Study
Les données qui suivent sont extraites de la cohorte des patients inclus dans l'étude CRASH2. Cette réinterprétation des données a pour objectif d'analyser le lien entre la mortalité à 28 jours et la transfusion de CGR. Les auteurs retrouvent un effet délétère de la transfusion de CGR pour les patients les moins à risque de mortalité. Ceci est en faveur des démarches de stratégies transfusionnelles sinon restrictives du moins raisonnées en fonction du contexte notamment préhospitalier où cette pratique associée à l'apport de fractions coagulantes semble être d'un grand intérêt(1).
Haemorrhage is a common cause of death in trauma patients. Although transfusions are extensively used in the care of bleeding trauma patients, there is uncertainty about the balance of risks and benefits and how this balance depends on the baseline risk of death. Our objective was to evaluate the association of red blood cell (RBC) transfusion with mortality according to the predicted risk of death.
Methods and Findings:
A secondary analysis of the CRASH-2 trial (which originally evaluated the effect of tranexamic acid on mortality in trauma patients) was conducted. The trial included 20,127 trauma patients with significant bleeding from 274 hospitals in 40 countries. We evaluated the association of RBC transfusion with mortality in four strata of predicted risk of death: ,6%, 6%–20%, 21%–50%, and .50%. For this analysis the exposure considered was RBC transfusion, and the main outcome was death from all causes at 28 days. A total of 10,227 patients (50.8%) received at least one transfusion. We found strong evidence that the association of transfusion with all-cause mortality varied according to the predicted risk of death (p-value for interaction ,0.0001). Transfusion was associated with an increase in all-cause mortality among patients with , 6% and 6%–20% predicted risk of death (odds ratio [OR] 5.40, 95% CI 4.08–7.13, p,0.0001, and OR 2.31, 95% CI 1.96–2.73, p,0.0001, respectively), but with a decrease in all-cause mortality in patients with .50% predicted risk of death (OR 0.59, 95% CI 0.47–0.74, p,0.0001). Transfusion was associated with an increase in fatal and non-fatal vascular events (OR 2.58, 95% CI 2.05–3.24, p,0.0001). The risk associated with RBC transfusion was significantly increased for all the predicted risk of death categories, but the relative increase was higher for those with the lowest (,6%) predicted risk of death (p-value for interaction ,0.0001). As this was an observational study, the results could have been affected by different types of confounding. In addition, we could not consider haemoglobin in our analysis. In sensitivity analyses, excluding patients who died early; conducting propensity score analysis adjusting by use of platelets, fresh frozen plasma, and cryoprecipitate; and adjusting for country produced results that were similar.
The association of transfusion with all-cause mortality appears to vary according to the predicted risk of death. Transfusion may reduce mortality in patients at high risk of death but increase mortality in those at low risk. The effect of transfusion in low-risk patients should be further tested in a randomised trial.
Trauma-induced coagulopathy: impact of the early coagulation support protocol on blood product consumption, mortality and costs
Le damage control resuscitation fait largement appel à l'apport de plasma, concentrés de globules rouges et de plaquettes dans un rapport de 1/1/1 (1). Malgré la relative correction de la coagulopathie la survie à long terme ne semble pas être améliorée (2). Aussi certains proposent d'avoir plutôt recours à l'administration précoce de fibrinogène plutôt que l'administration de plasma. Le travail suivant qui propose l'apport précoce de 2g de fibrinogène est en faveur d'une telle démarche.
Hemorrhage is the principal cause of death in the first few hours following severe injury. Coagulopathy is a frequent complication of critical bleeding. A network of Italian trauma centers recently developed a protocol to prevent and treat trauma-induced coagulopathy. A pre-post cohort multicenter study was conducted to assess the impact of the early coagulation support (ECS) protocol on blood products consumption,mortality and treatment costs.
We prospectively collected data from all severely injured patients (Injury Severity Score (ISS) >15) admitted to two trauma centers in 2013 and compared these findings with the data for 2011. Patients transfused with at least 3 units of packed red blood cells (PRBCs) within 24 hours of an accident were included in the study. In 2011, patients with significant hemorrhaging were treated with early administration of plasma with the aim of achieving a high (≥1:2) plasma-to-PRBC ratio. In 2013, the ECS protocol was the treatment strategy. Outcome data, blood product consumption and treatment costs were compared between the two periods.
The two groups were well matched for demographics, injury severity (ISS: 32.9 in 2011 versus 33.6 in 2013) and clinical and laboratory data on admission. In 2013, a 40% overall reduction in PRBCs was observed, together with a 65% reduction in plasma and a 52% reduction in platelets. Patients in the ECS group received fewer blood products: 6.51 units of PRBCs versus 8.14 units. Plasma transfusions decreased from 8.98 units to 4.21 units (P <0.05), and platelets fell from 4.14 units to 2.53 units (P <0.05). Mortality in 2013 was 13.5% versus 20% in 2011 (13 versus 26 hospital deaths, respectively) (nonsignificant). When costs for blood components, factors and point-of-care tests were compared, a €76,340 saving in 2013 versus 2011 (23%) was recorded.
The introduction of the ECS protocol in two Italian trauma centers was associated with a marked reduction in blood product consumption, reaching statistical significance for plasma and platelets, and with a non-significant trend toward a reduction in early and 28-daymortality. The overall costs for transfusion and coagulation support (including point-of-care tests) decreased by 23% between 2011 and 2013.
Is limited prehospital resuscitation with plasma more beneficial than using a synthetic colloid? An experimental study in rabbits with parenchymal bleeding
Il existe de grands débats sur la manière optimale d'assurer le remplissage vasculaire des blessés de guerre. Pour certains le fluide de référence est un hydroxyéthylamidon, pour d'autres un cristalloïde isotonique et en ce qui nous concerne les deux avec la mise en avant du sérum salé hypertonique premier suivi d'HEA. Actuellement il existe une tendance à promouvoir une autre stratégie faisant appel pour les blessés les plus graves au plasma voire la transfusion de sang frais. L'étude proposée avait pour objectif de confirmer l'intérêt d'une démarche "plasma premier". Une des surprises a été de constater que ce n'est pas cette dernière qui permettait d'obtenir le meilleur taux de survie mais l'emploi d'albumine, et ce de loin. Ces données expérimentales certes très partielles permettent aux auteurs (?) de rediscuter les conclusions de travaux anciens notamment de l'étude SAFE (1,2). Les solutés d'albumine utilisés par cette dernière ont une osmolarité de 260 mosm/kg (versus 305 mosm/kg pour le sérum salé). Les effets délétères notamment chez le traumatisé crânien pourraient être dus non pas à l'extravasation d'albumine dans le parenchyme cérébral lésé mais à l'hypoosmolarité de l'albumex 4%, ces deux mécanismes concourrant à la plus grande fréquence d'HTIC dans le groupe albumine (3). A méditer
Reports of survival benefits of early transfusion of plasma with red blood cells (1:1 ratio) in trauma patients suggest that plasma may be a better fluid to replace Hextend for battlefield resuscitation. We studied possible advantages of prehospital resuscitation with plasma compared with Hextend or albumin in a model of uncontrolled hemorrhage.
Male New Zealand white rabbits (3.3 T 0.1 kg) were anesthetized, instrumented, and subjected to a splenic injury with uncontrolled bleeding. Ten minutes after injury (mean arterial pressure [MAP] G 40 mm Hg), the rabbits received small and equal volumes (15 mL/kg) of rabbit plasma (n = 10), Hextend (n = 10), or 5% human albumin (n = 9) or no fluid. Fluids were administered in two bolus injections (20 minutes apart) and targeted to aMAP of 65 mm Hg. Animals were monitored for 2.5 hours or until death, and their blood losses were measured. Arterial blood samples were collected at different times and analyzed for ABG, CBC, and coagulation tests.
There were no differences in baseline measures among groups. Splenic injury caused similar hemorrhages (9.1 T 0.4 mL/kg at 10 minutes) and decreased MAP in all subjects. Subsequent resuscitation initiated additional bleeding. At 60 minutes after injury (20 minutes after resuscitation), longer activated partial thromboplastin time and lower fibrinogen concentrations were apparent compared with baseline values with differences among groups. Thrombelastography analysis indicated faster and stronger clot formation with plasma and albumin resuscitation than with Hextend use. Shock indices were increased in all groups, but smaller changes were measured in the albumin group. Total blood loss did not differ among resuscitated rabbits but was higher (p G 0.05) than among nonresuscitated animals. Survival rates were 11% (untreated), 40% (Hextend and plasma), and 89% (albumin, p G 0.05).
Resuscitation with plasma or albumin better preserved coagulation function than did Hextend. However, despite these improvements, plasma resuscitation did not reduce blood loss or improve survival, while albumin administration seemed beneficial
Treatment with a histone deacetylase inhibitor, valproic acid, is associated with increased platelet activation in alarge animal model of traumatic brain injury and hemorrhagic shock
Le concept du damaged control resuscitation fait appel en partie à de nouvelles modalités transfusionnelles et d'emploi de fractions coagulantes. D'autres approches sont possibles comme celles visant à restuarer la fonction plaquettaire. C'est ce que permettrait l'adminsitration de médicaments appartenant à la classe des inhibiteurs des histone deacetylase et dont les effets neuroprotecteurs pourraient ainsi être mis à profit. Le document proposé semble conforter cette approche.
We have previously shown that resuscitation with fresh frozen plasma (FFP) in a large animal model of traumatic brain injury (TBI) and hemorrhagic shock (HS) decreases the size of the brain lesion, and that addition of a histone deacetylase inhibitor, valproic acid (VPA), provides synergistic benefits. In this study, we hypothesized that VPA administration would be associated with a conservation of platelet function as measured by increased platelet activation after resuscitation.
MATERIALS AND METHODS:
Ten swine (42-50 kg) were subjected to TBI and HS (40% blood loss). Animals were left in shock for 2 h before resuscitation with either FFP or FFP+VPA (300 mg/kg). Serum levels of platelet activation markers transforming growth factor beta, CD40 L, P-selectin, and platelet endothelial cell adhesion molecule (PECAM) 1 were measured at baseline, postresuscitation, and after a 6-h observation period. Platelet activation markers were also measured in the brain whole cell lysates and immunohistochemistry.
Circulating P-selectin levels were significantly higher in the FFP+VPA group compared with the FFP alone group (70.85±4.70 versus 48.44±7.28 ng/mL; P<0.01). Likewise, immunohistochemistry data showed elevated P-selectin in the VPA treatment group (22.30±10.39% versus 8.125±3.94%, P<0.01). Serum sCD40L levels were also higher in the FFP+VPA group (3.21±0.124 versus 2.38±0.124 ng/mL; P<0.01), as was brainsCD40L levels (1.41±0.15 versus 1.22±0.12 ng/mL; P=0.05). Circulating transforming growth factor beta levels were elevated in the FFP+VPA group, but this did not reach statistical significance (11.20±1.46 versus 8.09±1.41 ng/mL; P=0.17). Brain platelet endothelial cell adhesion molecule 1 levels were significantly lower in the FFP+VPA group compared with the FFP group (5.22±2.00 pg/mL versus 7.99±1.13 pg/mL; P=0.03).
In this clinically relevant large animal model of combined TBI+HS, the addition of VPA to FFP resuscitation results in an early upregulation of platelet activation in the circulation and the brain. The previously observed neuroprotective effects of VPA may be due to a conservation of platelet function as measured by a higher platelet activation response after resuscitation.
1. Elle est fréquente voire très fréquente: Greuters et al. Critical Care 2011 15:R2 doi:10.1186/cc9399
2. Elle est + fréquente en cas d'hypoTA: Wafaisade Neurocrit Care. 2010 Apr;12(2):211-9
3. Elle est de mauvais pronostic: J Emerg Trauma Shock. 2013 Jul-Sep; 6(3): 180–185
4. Elle est mise en évidence plutôt par thromboélastographie (r TEG) : Sixta al., J Neurol Neurophysiol 2014, 6:5
Changing Patterns of In-Hospital Deaths Following Implementation of Damage Control Resuscitation Practices in US Forward Military Treatment Facilities
Analysis of combat deaths provides invaluable epidemiologic and quality-improvement data for trauma centers and is particularly important under rapidly evolving battlefield conditions.
To analyze the evolution of injury patterns, early care, and resuscitation among patients who subsequently died in the hospital, before and after implementation of damage control resuscitation (DCR) policies.
Design, Setting, and participants
In a review of the Joint Theater Trauma Registry (2002-2011) of US forward combat hospitals, cohorts of patients with vital signs at presentation and subsequent in-hospital death were grouped into 2 time periods: pre-DCR (before 2006) and DCR (2006-2011).
Main outcomes and measures
Injury types and Injury Severity Scores (ISSs), timing and location of death, and initial (24-hour) and total volume of blood products and fluid administered.
Of 57 179 soldiers admitted to a forward combat hospital, 2565 (4.5%) subsequently died in the hospital. The majority of patients (74%) were severely injured (ISS > 15), and 80% died within 24 hours of admission. Damage control resuscitation policies were widely implemented by 2006 and resulted in a decrease in mean 24-hour crystalloid infusion volume (6.1-3.2 L) and increased fresh frozen plasma use (3.2-10.1 U) (both P < .05) in this population. The mean packed red blood cells to fresh frozen plasma ratio changed from 2.6:1 during the pre-DCR period to 1.4:1 during the DCR period (P < .01). There was a significant increase in mean ISS between cohorts (pre-DCR ISS = 23 vs DCR ISS = 27; P < .05) and a marked shift in injury patterns favoring more severe head trauma in the DCR cohort.
Conclusions and relevance
There has been a significant shift in resuscitation practices in forward combat hospitals indicating widespread military adoption of DCR. Patients who died in a hospital during the DCR period were more likely to be severely injured and have a severe brain injury, consistent with a decrease in deaths among potentially salvageable patients
Both acute delivery of and storage with magnesium sulfate promote cold-stored platelet aggregation and coagulation function
Il y a quelque mois était publié un travail de recherche portant sur l'intérêt de l'administration de Adénosine/Lidocaïne/Mg2+ ALM (1, 2, 3). Une hypothèse faite par les auteurs serait que L'ALM agirait comme un antifibrinolytique en activant la voie du thrombin-activatable fibrinolysis inhibitor (TAFI) plutôt que celle de la protéine C. Cette action passerait par un mécanisme antiinflammatoire, une modification de la polarité endothéliale et une action sur la fonction plaquettaire. Le travail expérimental dont l'abstract est présenté met en avant l'intérêt de l'adminsitration de magnésium pour la restauration de la fonction plaquettaire après conservation de palquettes d'aphérèse au delà de 5 jours.
The platelet storage lesion causes loss of function and viability over time. A new paradigm for platelet storage is desired to enable safer, more effective transfusions while reducing waste. We hypothesized that repletion of Mg, which is chelated by citrate anticoagulant, could reduce platelet storage lesion severity when given in conjunction with storage at a refrigerated temperature.
Apheresis platelet units were collected from healthy donors and stored at 22°C or 4°C. On Days 0, 2, 4, and 8, samples were collected for analyses of receptor-mediated aggregation, coagulation, adhesion to collagen under flow, and viability. In the first series, samples were given anacute dose of MgSO4 before testing; in the second series, storage bags were supplemented with 0-, 3-, or 6-mM MgSO4.
Acutely delivered MgSO4 induced a more rapid coagulation time in apheresis platelets, further enhanced by storage at 4°C. Plateletadhesion to a collagen surface while exposed to arterial shear rates (920 s) was enhanced by MgSO4 supplementation-acute MgSO4 had a large effect on adhesion of fresh platelets, which diminished more rapidly in 22°C samples, while storage with MgSO4 showed significant benefits even out to Day 4 at both temperatures. Although 4°C storage improves the longevity of platelet aggregation responses to agonists, MgSO4 supplementation did not change those responses.
Acute MgSO4 reduces clot time likely through the transient increase of free Ca. Limited differences between platelet function inacute delivery of and storage with MgSO4 diminish the possibility that Mg-induced metabolic inhibition of platelets synergizes with 4°C storage. Regardless, magnesium supplementation to platelets is an exciting possibility in transfusion because the adhesion response of 22°C-stored platelets on Day 4 is significantly enhanced when stored with 6-mM MgSO4
Trauma-Induced Coagulopathy: An Institution's 35 Year Perspective on Practice and Research
Association of Cryoprecipitate and Tranexamic Acid With Improved Survival Following Wartime Injury: Findings From the MATTERs II Study
Objective To quantify the impact of fibrinogen-containing cryoprecipitate in addition to the antifibrinolytic tranexamic acid on survival in combat injured.
Design Retrospective observational study comparing the mortality of 4 groups: tranexamic acid only, cryoprecipitate only, tranexamic acid and cryoprecipitate, and neither tranexamic acid nor cryoprecipitate. To balance comparisons, propensity scores were developed and added as covariates to logistic regression models predicting mortality.
Setting A Role 3 Combat Surgical Hospital in southern Afghanistan.
Patients A total of 1332 patients were identified from prospectively collected UK and US trauma registries who required 1 U or more of packed red blood cells and composed the following groups: tranexamic acid (n = 148), cryoprecipitate (n = 168), tranexamic acid/cryoprecipitate (n = 258), and no tranexamic acid/cryoprecipitate (n = 758).
Main Outcome Measure In-hospital mortality.
Results Injury Severity Scores were highest in the cryoprecipitate (mean [SD], 28.3 [15.7]) and tranexamic acid/cryoprecipitate (mean [SD], 26 [14.9]) groups compared with the tranexamic acid (mean [SD], 23.0 [19.2]) and no tranexamic acid/cryoprecipitate (mean [SD], 21.2 [18.5]) (P < .001) groups. Despite greater Injury Severity Scores and packed red blood cell requirements, mortality was lowest in the tranexamic acid/cryoprecipitate (11.6%) and tranexamic acid (18.2%) groups compared with the cryoprecipitate (21.4%) and no tranexamic acid/cryoprecipitate (23.6%) groups. Tranexamic acid and cryoprecipitate were independently associated with a similarly reduced mortality (odds ratio, 0.61; 95% CI, 0.42-0.89; P = .01 and odds ratio, 0.61; 95% CI, 0.40-0.94; P = .02, respectively). The combined tranexamic acid and cryoprecipitate effect vs neither in a synergy model had an odds ratio of 0.34 (95% CI, 0.20-0.58; P < .001), reflecting nonsignificant interaction (P = .21).
Conclusions Cryoprecipitate may independently add to the survival benefit of tranexamic acid in the seriously injured requiring transfusion. Additional study is necessary to define the role of fibrinogen in resuscitation from hemorrhagic shock.
Tuning Ligand Density on Intravenous Hemostatic Nanoparticles Dramatically Increases Survival Following Blunt Trauma
Explosions account for 79% of combat-related injuries, leading to multiorgan hemorrhage and uncontrolled bleeding. Uncontrolled bleeding is the leading cause of death in battlefield traumas as well as in civilian life. We need to stop the bleeding quickly to save lives, but, shockingly, there are no treatments to stop internal bleeding. A therapy that halts bleeding in a site-specific manner and is safe, stable at room temperature, and easily administered is critical for the advancement of trauma care. To address this need, we have developed hemostatic nanoparticles that are administered intravenously. When tested in a model of blast trauma with multiorgan hemorrhaging, i.v. administration of the hemostatic nanoparticles led to a significant improvement in survival over the short term (1 h postblast). No complications from this treatment were apparent out to 3 wk. This work demonstrates that these particles have the potential to save lives and fundamentally change trauma care.
Early treatment with lyophilized plasma protects the brain in a large animal model of combined traumatic brain injury and hemorrhagic shock
Imam AM et Al. J Trauma Acute Care Surg. 2013;75: 976-983
Bien sûr une étude animale, mais une de plus qui milite pour un emploi précoce du plasma lyophylisé.
BACKGROUND: Combination of traumatic brain injury (TBI) and hemorrhagic shock (HS) can result in significant morbidity and mortality. We have previously shown that early administration of fresh frozen plasma (FFP) in a large animal model of TBI and HS reduces the size of the brain lesion as well as the associated edema. However, FFP is a perishable product that is not well suited for use in the austere prehospital settings. In this study, we tested whether a shelf-stable, low-volume, lyophilized plasma (LSP) product was as effective as FFP.
Yorkshire swine (42-50 kg) were instrumented to measure hemodynamic parameters, intracranial pressure, and brain tissue oxygenation. A prototype, computerized, cortical impact device was used to create TBI through a 20-mm craniotomy: 15-mm cylindrical tipimpactor at 4 m/s velocity, 100-millisecond dwell time, and 12-mm penetration depth. Volume-controlled hemorrhage was induced(40-45% total blood volume) concurrent with the TBI. After 2 hours of shock, animals were treated with (1) normal saline (NS, n = 5), (2) FFP (n = 5), and (3) LSP (n = 5). The volume of FFP and LSP matched the shed blood volume, whereas NS was 3 times the volume. Six hours after resuscitation, brains were sectioned and stained with TTC (2, 3, 5-Triphenyltetrazolium chloride), and lesion size (mm3) and swelling (percent change in volume compared with the contralateral, uninjured side) were measured.
This protocol resulted in a highly reproducible brain injury, with clinically relevant changes in blood pressure, cardiac output, tissue hypoperfusion, intracranial pressure, and brain tissue oxygenation. Compared with NS, treatment with LSP significantly ( p G 0.05) decreased brain lesion size and swelling (51% and 54%, respectively).
CONCLUSION: In a clinically realistic combined TBI + HS model, early administration of plasma products decreases brain lesion size and edema. LSP is as effective as FFP, while offering many logistic advantages.
Point-of-injury use of reconstituted freeze dried plasma as a resuscitative fluid: A special report for prehospital trauma care
Glassberg E. et All. J J Trauma Acute Care Surg. 2013;75(Suppl 2):S111YS111.
La prise en charge d'hémorrragie catastrophique en phase préhospitalière est particulièrement complexe. Ces dernières années la mise en place d'un réseau structuré de prise en charge, 'application de procédures spécifiques visant à arrêter les hémorragies au plus tôt, le recours à l'acide tranexaminique, la prévention des hypothermies et l'application d'une politique raisonnée de rénaimation/chirurgie ont constitué une grande avancée. Certaines nations ont équipé leurs vecteurs d'évacuations de concentrés érythrocytaires. Le maintien d'une coagulation optimale est un enjeu majeur. Pour cela existe, entre autres, le plasma lyophilisé. Les forces armées israéliennes militent pour l'emploi de ce type de solutions en phase préhospitalière
Case Scenario: Management of Trauma-induced Coagulopathy in a Severe Blunt Trauma Patient
Un point très clair du problème
Une econférence qui fait parfaitement le point sur l'intérêt et les questions en suspens concernant l'intérêt du fibrinogène dans la réanimation hémostatique du traumasié qui saigne.
En condition de combat avant l'arivée en structure hopsitalière de campagne, l'apport de fibrinogène peut être réalisé par l'apport de plasma lyophylisé (PLYO) produit par le SSA (obtenu en moins de 6 min après reconstitution à température ambiante par adjonction d'eau PPI, chaque unité contient au moins 0,5g de fibrinogène). C'est une des composantes de la transfusion de plasma thérapeutique. qui doit désormais être envisagé au niveau du role 1 (poste de secours ou vecteur d'évacuation tactique).
Il ne peut (pour des raisons de logistique de production et de disponibilté) être apporté qu'à partir de la prise en charge hospitalière.
Pour approfondir avec en perspective le blessé de guerre hémorragique:
(1) Un revue générale sur la coagulopathie de l'hémorragie massive: "Hemodilution caused by trauma and major surgery induces complex hemostatic changes involving procoagulant factors as well as anticoagulant, fibrinolytic, and antifibrinolytic factors. The endothelial responses to shear stress, active proteases, and various inflammatory cells and cytokines add further complexity to the pathophysiology of massive hemodilution. In addition to the conventional transfusion products, which are often difficult to administer in a timely manner, purified factor concentrates of plasma origin and from recombinant synthesis are highly concentrated (i.e., small volume) for a rapid restoration of targeted factor(s). The use of point-of-care testing is desirable to optimize the dose and timing of such intervention. Additional clinical trials of different factor concentrate therapies are required to validate their efficacy and safety in patients after trauma or major surgery.152 Further understanding of the time course of pathophysiological changes in massive hemodilution is necessary to optimally balance hemostatic and anticoagulant therapies."
(2) Un focus sur le blessé de guerre: "In patients with combatrelated trauma requiring massive transfusion, the transfusion of an increased fibrinogen: RBC ratio was independently associated with improved survival to hospital discharge, primarily by decreasing death from hemorrhage. Prospective studies are needed to evaluate the best source of fibrinogen and the optimal empiric ratio of fibrinogen to RBCs in patients requiring massive transfusion."
(3) La stratégie transfusionnelle du blessé de guerre SFAR 2012: " En traumatologie, l’administration de fibrinogène est recommandée : dose initiale de 3 à 4 g suivie d’une administration régulière en cas d’hypofibrinogènémie biologique (<1,5 à 2 g/l) ou de signes thromboelastométriques de déficit fonctionnel en fibrinogène . Une analyse nord-américaine rétrospective de 252 dossiers de BdG ayant nécessité une TM a permis de mettre en évidence qu’un apport faible de fibrinogène (< 0,2 g/CGR) au cours de la transfusion était associé à une majoration significative de la mortalité de ces blessés . Le SSA américain utilise l’apport de cryoprécipités contenant surtout du fibrinogène et d’autres facteurs de coagulation pour compenser ces déficits . Les recommandations du SSA français sont l’administration de fibrinogène de façon répétée afin de maintenir un fibrinogène plasmatique supérieur à 1,5 g/l ou en l’absence de laboratoire (situation des structures chirurgicales « légères »), d’administrer au moins 0,2 g de fibrinogène par CGR transfusé."
Use of recombinant factor VIIA for control of combat-related haemorrhage.
Ce travail met en exergue que le recours au FVIIa n'a pas d'intérêt prouvé en cas de prise en charge de traumatismes pénétrants. Ceci est d'autant plus vrai qu'il est fait alors qu'une coagulopathie sévère est installée (The utility of recombinant factor VIIa as a last resort in trauma. Mamtani R. et all. World Journal of Emergency Surgery 2012, 7(Suppl 1):S7)
Recombinant activated human coagulation factor VII (rFVIIa), an intravascular strategy to promote clotting, is being used as an adjunct to surgical control of bleeding in combat trauma patients.
To describe the initial experiences with rFVIIa administered to combat casualties at US Navy-Marine Corps medical treatment facilities in Iraq, and to comparesurvival outcomes of those treated with rFVIIa to controls not receiving rFVIIa.
Medical encounter data from the US Navy-Marine Corps Combat Trauma Registry were retrospectively reviewed to identify all battle-injured patients documented as having received rFVIIa during the period May 2004 to January 2006 of Operation Iraqi Freedom. Available clinical and injury related data are presented to characterise the patients. To assess effects of rFVIIa on survival outcomes, rFVIIa cases were matched to controls on injury severity and age.
22 battle-injured patients from the Combat Trauma Registry received rFVIIa. Primarily young US Marines, these patients typically had penetrating injuries from improvised explosive devices and gunshot wounds. Injuries were often abdominal. The average dose used was similar to that reported in another study of civilian trauma patients, although dosing varies widely in the existing experimental and anecdotal literature. Over two-thirds (68%) of the rFVIIa patients surviveddan identical outcome seen for a matched control group of 22 patients.
Survival of seriously injured combat casualties was good, although identical to that of a control group. Methodological limitations of this retrospective study preclude making firm conclusions about the effectiveness of rFVIIa. Future controlled studies are needed for safety and efficacy testing of rFVIIa in combat trauma patients.