Sylvain Ausset

Use of freeze-dried plasma in French intensive care unit in Afghanistan.

BACKGROUND Modern warfare causes severe injuries, and despite rapid transportation to theater regional trauma centers, casualties frequently arrive coagulopathic and in shock. Massive hemorrhage management includes transfusion of red blood cells and plasma in a 1:1 ratio. Fresh frozen plasma requires thawing and badly fits the emergency criteria. Since 1994, the French Military Blood Bank has been producing freeze-dried plasma (FDP) and providing it for overseas operation. The aim of our study was to evaluate the use of FDP in war settings and to assess its clinical efficiency and safety. PATIENTS We performed a prospective study of the FDP delivered at the International Security Assistance Force Role 3 Military Medical Treatment Facility in the Kabul Afghanistan International Airport between February 2010 and February 2011. We included every patient who received at least one unit of FDP. Basic clinical data were recorded at admission. Transfusion requirements were monitored. Biological testing were performed before and after administration of FDP including hemoglobin concentration, platelets count, fibrinogen level, prothrombin time (PT), and thromboelastography. RESULTS Eighty-seven casualties received FDP during 93 episodes of transfusion. On average, 3.5 FDP units were transfused per episodes of transfusion. Of the 87 patients studied, 7 died because of nonsurvivable injuries and outcomes were unavailable for 11. The other 59 patients survived. PT significantly declined by an average of 3.3 seconds after FDP transfusion. This moderate decrease in PT reflects continued bleeding and resuscitation. It nevertheless suggests improvement in hemostasis before surgical control of bleeding. All FDP users reported ease of use, clinically observed efficacy equivalent to fresh frozen plasma and the absence of adverse effects associated with FDP. CONCLUSION Our results provide evidence of the effectiveness of FDP for the prevention or correction of coagulopathy and hemorrhage in combat casualties.

The Evolving Role of Lyophilized Plasma in Remote Damage Control Resuscitation in the French Armed Forces Health Service

Freeze‐dried plasma was developed by the US Army for the resuscitation of combat casualties during World War II. The French Military Blood Institute began producing French lyophilized plasma (FLYP) in 1949, in accordance with French blood product guidelines. Since 2010, a photochemical pathogen inactivation process has been implemented to reduce the remaining transfusion‐related infectious risk. All quality controls for this procedure verify that the hemostatic properties of FLYP are conserved. FLYP is compatible with all blood types, can be stored at room temperature for 2 years, and its reconstitution requires less than 6 minutes. As a result, FLYP allows quick delivery of all the coagulation proteins and the application of a 1:1 ratio of FLYP and red blood cells in the context of a massive transfusion. Hemovigilance data collected in France since 1994 have included FLYP. Results indicate no reporting of infection related to the use of FLYP. Clinical monitoring with a focus on hemostasis was implemented in 2002 and expanded in 2010. The data, obtained from overseas operations, confirmed the indications, the safety and the clinical efficacy of FLYP. Further research is needed to determine specific indications for FLYP in the therapeutic management of civilian patients with severe hemorrhage.

Quality of postoperative care after major orthopedic surgery is correlated with both long-term cardiovascular outcome and troponin Ic elevation.

Background:The aim of this study performed in patients undergoing major orthopedic surgery was to assess the impact of changes in practice on both the incidence of postoperative myocardial ischemia (PMI) detected by serial measurements of troponin Ic and long-term cardiac outcome. Methods:During a 3-yr period, troponin Ic was measured on the first 3 days after major orthopedic surgery in a multidisciplinary hospital. After 16 months of study, postoperative care was improved. Cardiac death, myocardial infarction, and cardiac failure were considered major adverse cardiac events and were recorded during the hospital stay and the first postoperative year. The incidences of PMI and major adverse cardiac events were used as result indicators for quality of care and compared before (P1) and after (P2) quality enhancement. Results:Three hundred seventy-eight surgical procedures were included (P1, 123; P2, 255). Incidences of PMI and major adverse cardiac events were 8.9 versus 3.9% (P = 0.04) and 8.1 versus 1.9% (P = 0.004) for P1 and P2, respectively. Using a multivariate Cox regression analysis adjusted for baseline data, independent factors associated with the occurrence of a major adverse cardiac event were phase P1 (hazard ratio = 4.5; 97.8% confidence interval [CI], 1.1–17.4) and PMI (Hazard ratio = 6.4; 97.8% CI, 1.6–26.4). Conclusions:Our postoperative care policy after major orthopedic surgery strongly correlated with both short-term cardiac outcome (i.e., PMI with troponin Ic release) and long-term cardiac outcome. Thus, in a given surgical population, variation of incidence of troponin Ic elevations could be used as a result indicator for postoperative care policy.

Tranexamic acid as part of remote damage-control resuscitation in the prehospital setting: A critical appraisal of the medical literature and available alternatives.

BACKGROUND Hemorrhage remains the leading cause of preventable trauma-associated mortality. Interventions that improve prehospital hemorrhage control and resuscitation are needed. Tranexamic acid (TXA) has recently been shown to reduce mortality in trauma patients when administered upon hospital admission, and available data suggest that early dosing confers maximum benefit. Data regarding TXA implementation in prehospital trauma care and analyses of alternatives are lacking. This review examines the available evidence that would inform selection of hemostatic interventions to improve outcomes in prehospital trauma management as part of a broader strategy of “remote damage-control resuscitation” (RDCR). METHODS The medical literature available concerning both the safety and the efficacy of TXA and other hemostatic agents was reviewed. RESULTS TXA use in surgery was studied in 129 randomized controlled trials, and a meta-analysis was identified. More than 800,000 patients were followed up in large cohort study. In trauma, a large randomized controlled trial, the CRASH-2 study, recruited more than 20,000 patients, and two cohort studies studied more than 1,000 war casualties. In the prehospital setting, the US, French, British, and Israeli militaries as well as the British, Norwegian, and Israeli civilian ambulance services have implemented TXA use as part of RDCR policies. CONCLUSION Available data support the efficacy and the safety of TXA. High-level evidence supports its use in trauma and strongly suggests that its implementation in the prehospital setting offers a survival advantage to many patients, particularly when evacuation to surgical care may be delayed. TXA plays a central role in the development of RDCR strategies.

In vitro hemostatic properties of French lyophilized plasma.

Background: French lyophilized plasma (FLyP) is used routinely by the French Armed Forces in war settings. The authors compared concentrations of coagulation proteins and global in vitro hemostatic properties in FLyP and in the same plasma before lyophilization to assess the impact of lyophilization on coagulation properties. Methods: Twenty-four batches of plasma before and after lyophilization were tested for coagulation proteins. Thrombin generation time, thrombin antithrombin concentration, prothrombin fragment 1 + 2, and thromboelastography were assessed. Finally, the efficiencies of FLyP and plasma before lyophilization were compared on a hemorrhagic shock hemodilution model and tested on TEG®(Haemoscope Corporation, Glenview, IL). Results: Prothrombin time ratio (1.1 ± 0.1 vs. 1.2 ± 0.1) and activated partial thromboplastin time (35 ± 1.3 vs. 39 ± 2.4 s) were significantly increased in FLyP (8 ± 3%, P < 0.05 and 11 ± 5%, P < 0.001, respectively). Activity of factors V (85 ± 18 vs. 51 ± 16 UI/ml) and VIII (0.77 ± 0.11 vs. 0.62 ± 0.10 UI/ml) was also diminished (25 ± 12% and 20 ± 7%, respectively); however, activity of other factors was preserved. The authors observed no alteration in the thromboelastographic parameters. Thrombin generation was preserved when induced with 5 pM tissue factor in vitro but significantly reduced when using 1 pM tissue factor. The thrombin-antithrombin complex and prothrombin fragment 1 + 2 attested for the absence of coagulation activation. This hemodilution model showed no significant difference before and after lyophilization. Conclusions: The study results account for a significant decrease of factors V and VIII in FLyP. However, the global capacity to induce clot formation in vitro seems to be preserved. The clinical relevance of these decreased factors is not known.

Freeze dried plasma: a French army specialty

We read with interest the article by Nascimento and colleagues [1] on fresh frozen plasma (FFP) in massive bleedings. We fully agree with their conclusion when they say that we need immediately available universal donor AB plasma. Hemorrhagic shock is the primary cause of avoidable mortality in combatants. Data from the recent US army war experience show clearly that in cases of massive transfusion the transfusion policy strongly impacts mortality. Namely, for massive bleeding the ratio between red blood cells and clotting factors should be close to the composition of whole blood [2]. Plasma is thus essential for massive transfusions. But FFP use is impractical in uncertain environments such as a battlefi eld. During military operations, refrigerated transportation and storage are logistical problems. Th awing of FFP takes a long time, with an important loss of plasma in austere environments. For example, Mabry and colleagues [3] report that, during the Mogadishu urban battle, the available FFP was stored in bags that fractured one-third of the time upon thawing. For these reasons, the French army has used freezedried and secured plasma (FDSP) since 1994. Plasma separated from fresh blood of at least ten donors is lyophilized to produce FSDP. Blood type selection allows the dilution and neutralization of natural anti-A and antiB hemagglutinins. Th is FDSP is thus compatible with any blood type. In addition, FDSP is shelf-stable in ambient temperatures for 2 years and easily rehydrated with 200 ml of water for injections in less than 3 minutes, allowing immediate provision with the fi rst packed red blood cells [4]. FDSP contains all clotting factors and proteins. After more than 2 years storage at ambient temperature, the fi brinogen and clotting factor levels of FDSP are equivalent to FFP [4]. Th e securization process is quarantine (i.e. the plasma is held until the donor returns and is retested after a period that is longer than the window period of known viruses). Plasma as FDSP is thus a logistically superior product, without compromising hemostatic properties, quickly available in cases of emergency for any blood type.

Postoperative myocardial damages after hip fracture repair are frequent and associated with a poor cardiac outcome: a three-hospital study

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La transfusion en situation d’exception, expérience du service de santé des armées

Blood transfusion is required in a number of emergency settings and the French military health service (FMHS) has issued specific guidelines for the treatment of war casualties. These guidelines take into account European standards and laws, NATO standards, and also public sentiment regarding transfusion. These guidelines reflect a determination to control the process and to avoid the improvisation frequently associated with wartime transfusion. The evolution in warfare (terrorism and bombing more frequent than gunshot) and the wide use of body armor have deeply changed the clinical presentation of war injuries. These now involve the extremities in 80% of cases, with extensive tissue damage and heavy blood loss. The FMHS recommends that war casualties with hemorrhagic shock be brought quickly to a medical treatment facility (MTF) after first-line treatment applied through buddy aid or by medics. In the MTF, before an early Medevac, a damage control surgery will be performed, with resuscitation using freeze-dried plasma, red blood cells and fresh whole blood. The French military blood bank is responsible for blood product supply, training and medical advice regarding transfusion therapy during wartime, as well as hemovigilance. All transfusion therapy practices are periodically assessed but research on whole blood pathogen reduction is being conducted in order to reduce the residual infectious risk associated with this product.

A Serious Game for Massive Training and Assessment of French Soldiers Involved in Forward Combat Casualty Care (3D-SC1): Development and Deployment.

Background The French Military Health Service has standardized its military prehospital care policy in a ‘‘Sauvetage au Combat’’ (SC) program (Forward Combat Casualty Care). A major part of the SC training program relies on simulations, which are challenging and costly when dealing with more than 80,000 soldiers. In 2014, the French Military Health Service decided to develop and deploy 3D-SC1, a serious game (SG) intended to train and assess soldiers managing the early steps of SC. Objectives The purpose of this paper is to describe the creation and production of 3D-SC1 and to present its deployment. Methods A group of 10 experts and the Paris Descartes University Medical Simulation Department spin-off, Medusims, coproduced 3D-SC1. Medusims are virtual medical experiences using 3D real-time videogame technology (creation of an environment and avatars in different scenarios) designed for educational purposes (training and assessment) to simulate medical situations. These virtual situations have been created based on real cases and tested on mannequins by experts. Trainees are asked to manage specific situations according to best practices recommended by SC, and receive a score and a personalized feedback regarding their performance. Results The scenario simulated in the SG is an attack on a patrol of 3 soldiers with an improvised explosive device explosion as a result of which one soldier dies, one soldier is slightly stunned, and the third soldier experiences a leg amputation and other injuries. This scenario was first tested with mannequins in military simulation centers, before being transformed into a virtual 3D real-time scenario using a multi-support, multi–operating system platform, Unity. Processes of gamification and scoring were applied, with 2 levels of difficulty. A personalized debriefing was integrated at the end of the simulations. The design and production of the SG took 9 months. The deployment, performed in 3 months, has reached 84 of 96 (88%) French Army units, with a total of 818 hours of connection in the first 3 months. Conclusions The development of 3D-SC1 involved a collaborative platform with interdisciplinary actors from the French Health Service, a university, and videogame industry. Training each French soldier with simulation exercises and mannequins is challenging and costly. Implementation of SGs into the training program could offer a unique opportunity at a lower cost to improve training and subsequently the real-time performance of soldiers when managing combat casualties; ideally, these should be combined with physical simulations.

Déclinaisons militaires françaises des directives européennes en matière d'hémovigilance

European military transfusion services follow operational guidelines established by their respective national health systems and conform with European Union directives and NATO standards as applicable to member countries. Certain features are common to all of these standards, especially the pre-selection of volunteer, almost exclusively unpaid donors. NATO requirements are very close to European guidelines, with the exception that NATO permits the use of blood products collected in emergency conditions in theater when circumstances allow no better option. Blood product traceability exists for every country but is not always centralized or computerized. Serious adverse event reporting relies on national haemovigilance networks. Military considerations become important mainly in overseas operations, where the overall policy is to implement the relevant national, European or NATO guidelines with adjustments made for unique wartime circumstances and the risk/benefit ratio for the individual patient needing a transfusion.