19/12/2016
The 2015 Remote Damage Control Resuscitation Symposium
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18/12/2016
Coagulopathie traumatique. Données actuelles
Acute traumatic coagulopathy: pathophysiology and resuscitation.
Acute Traumatic Coagulopathy occurs immediately after massive trauma when shock, hypoperfusion, and vascular damage are present. Mechanisms for this acute coagulopathy include activation of protein C, endothelial glycocalyx disruption, depletion of fibrinogen, and platelet dysfunction. Hypothermia and acidaemia amplify the endogenous coagulopathy and often accompany trauma. These multifactorial processes lead to decreased clot strength, autoheparinization, and hyperfibrinolysis. Furthermore, the effects of aggressive crystalloid administration, haemodilution from inappropriate blood product transfusion, and prolonged surgical times may worsen clinical outcomes. We review normal coagulation using the cell-based model of haemostasis and the pathophysiology of acute traumatic coagulopathy. Developed trauma systems reduce mortality, highlighting critical goals for the trauma patient in different phases of care. Once patients reach a trauma hospital, certain triggers reliably indicate when they require massive transfusion and specialized trauma care. These triggers include base deficit, international normalized radio (INR), systolic arterial pressure, haemoglobin concentration, and temperature. Early identification for massive transfusion is critically important, as exsanguination in the first few hours of trauma is a leading cause of death. To combat derangements caused by massive haemorrhage, damage control resuscitation is a technique that addresses each antagonist to normal haemostasis. Components of damage control resuscitation include damage control surgery, permissive hypotension, limited crystalloid administration, haemostatic resuscitation, and correction of hyperfibrinolysis.
Fibrinogène dès que l'Hb baisse ?
Estimation of plasma fibrinogen levels based on hemoglobin, base excess and Injury Severity Score upon emergency room admission
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Il existe un grand débat sur la manière de prendre en charge la coagulopathie traumatique des traumatisés ballistiques en contexte d'isolement (1,2).Un des sujets porte sur la manière de corriger l'hypofibrinogénémie soit par apport de Plasma soit par apport de concentrés de fibrinogène (3, 4). Le consensus européen valide les deux approches (5). Mais dans notre contexte d'intervention quels critères d'administration appliquer ? L'hémoglobinémie à la prise en charge permettrait d'indiquer l'apport de fibrinogène, en gros dès qu'elle est abaissée et surtout <10g/dl. C'est ce que peut laisser penser cette étude. Des moyens simples utilisables en contexte d'isolement permettent donc de stratifier les indications de fibrinogène apporté soit sous forme concentré soit sous forme de plasma (6).
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INTRODUCTION:
Fibrinogen plays a key role in hemostasis and is the first coagulation factor to reach critical levels in massively bleeding trauma patients. Consequently, rapid estimation of plasma fibrinogen (FIB) is essential upon emergency room (ER) admission, but is not part of routine coagulation monitoring in many centers. We investigated the predictive ability of the laboratory parameters hemoglobin (Hb) and base excess (BE) upon admission, as well as the Injury Severity Score (ISS), to estimate FIB in major trauma patients.
METHODS:
In this retrospective study, major trauma patients (ISS ≥16) with documented FIB analysis upon ER admission were eligible for inclusion. FIB was correlated with Hb, BE and ISS, alone and in combination, using regression analysis.
RESULTS:
A total of 675 patients were enrolled (median ISS 27). FIB upon admission correlated strongly with Hb, BE and ISS.
Multiple regression analysis showed that Hb and BE together predicted FIB (adjusted R2 = 0.46; loge(FIB) = 3.567 + 0.223.Hb - 0.007.Hb2 + 0.044.BE), and predictive strength increased when ISS was included (adjusted R2 = 0.51; loge(FIB) = 4.188 + 0.243.Hb - 0.008.Hb2 + 0.036.BE - 0.031.ISS + 0.0003.ISS2). Of all major trauma patients admitted with Hb <12 g/dL, 74% had low (<200 mg/dL) FIB and 54% had critical (<150 mg/dL) FIB. Of patients admitted with Hb <10 g/dL, 89% had low FIB and 73% had critical FIB. These values increased to 93% and 89%, respectively, among patients with an admission Hb <8 g/dL. Sixty-six percent of patients with only a weakly negative BE (<-2 mmol/L) showed low FIB. Of patients with BE <-6 mmol/L upon admission, 81% had low FIB and 63% had critical FIB. The corresponding values for BE <-10 mmol/L were 89% and 78%, respectively.
CONCLUSIONS:
Upon ER admission, FIB of major trauma patients shows strong correlation with rapidly obtainable, routine laboratory parameters such as Hb and BE. These two parameters might provide an insightful and rapid tool to identify major trauma patients at risk of acquired hypofibrinogenemia. Early calculation of ISS could further increase the ability to predict FIB in these patients. We propose that FIB can be estimated during the initial phase of trauma care based on bedside tests.
14/12/2016
Fibrinogène: Moins de décès
Pre-emptive administration of fibrinogen concentrate contributes to improved prognosis in patients with severe trauma
Yamamoto K, et al. Trauma Surg Acute Care Open 2016;1:1–5
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Bien que cela reste encore discuté, l'apport précoce de fibrinogène améliorerait la survie des traumatisés sévères. Cette publication est du moins en faveur de cette hypothèse.
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Background
Patients with severe trauma often present with critical coagulopathy, resulting in impaired hemostasis, massive hemorrhage, and a poor survival prognosis. The efficacy of hemostatic resuscitation in correcting coagulopathy and restoring tissue perfusion has not been studied. We assessed a novel approach of pre-emptive administration of fibrinogen concentrate to improve critical coagulopathy in patients with severe trauma.
Methods
We retrospectively compared blood transfusion volumes and survival prognosis between three groups of patients with trauma, with an Injury Severity Score (ISS) ≥26 over three consecutive periods: group A, no administration of fibrinogen concentrate; group B, administration of 3 g of fibrinogen concentrate after evaluation of trauma severity and a plasma fibrinogen level <1.5 g/L; group C, pre-emptive administration of 3 g of fibrinogen concentrate immediately on patient arrival based on prehospital information, including high-severity injury or assessed
need for massive transfusion before measurement of fibrinogen.
Results
∼56% of patients with an ISS ≥26 and transfused with red blood cell concentrates ≥10 units, had hypofibrinogenemia (fibrinogen <1.5 g/L) on arrival. Patients who received fibrinogen concentrate in group C showed significantly higher fibrinogen levels after treatment with this agent than those in group B (2.41 g/L vs 1.88 g/L; p=0.01). Although no significant difference was observed in blood transfusion volumes between the groups, the 30-day survival of patients in group C (all, and those with an ISS ≥26) was significantly better than in group A ( p<0.05). The 48-hour mortality rate in patients with an ISS ≥26 was significantly lower in group C than in group A (8.6% vs 22.9%; p=0.005). Further, among patients with an ISS ≥41, the overall mortality was significantly lower in group C than in group A (20% vs 50%; p=0.02).
Conclusion
Pre-emptive administration of fibrinogen concentrate for patients with trauma with critical coagulopathy may contribute to improved survival.
| Tags : coagulopathie
11/12/2016
NaCl 7,5% ? A voir mais sans Colloïdes.
Pre-Hospital Resuscitation of Traumatic Hemorrhagic Shock with Hypertonic Solutions Worsen Hypo-Coagulation and Hyper-Fibrinolysis
Delano M. et Al. Shock. 2015 Jul;44(1):25-31
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Le choix d'un liquide de remplissage vasculaire n'est pas simple. Au delà des contraintes d'efficacité en termes de remplissage vasculaire, de bonne tolérance notamment rénale il y a également les effets de ce dernier sur la coagulation. On sait qu'une partie importante des blessés actuellement pris en charge présentent une coagulopathie traumatique (1). Le NaCl 7.5% est le soluté recommandé par la procédure du sauvetage au combat (2) car il représente le meilleur compromis intérêt médical/logistique. Le travail ici présenté met en évidence les effets délétères des solutés hypertoniques sur la coagulation. Ce document mérite cependant d'être pondéré car il s'appuie sur une petite cohorte de patients de traumatologie civile, que le profil du remplissage vasculaire préhospitalier n'est pas clairement rapporté hormis le premier liquide, qu'il ne précise pas le niveau de calcémie plasmatique car ce dernier peut être affecté selon la nature des solutés utilisés (4), que le groupe HS a des marqueurs d'hypoperfusion tissulaire identique au groupe NS, que la comparaison se fait avec un groupe de sujets sains et non entre les groupes. Par ailleurs on sait également qu'il est mis en avant l'intérêt des solutions HS en matière de prise en charge des HTIC des plaies cranio-cérébrales (4) et la réduction de l'activation des polynucléaires neutrophiles (5). Donc il ne s'agit pas de remettre en question le choix actuel, mais de le repositionner dans le débat notamment avec l'emploi du Plama lyophylisé comme soluté de remplissage premier des blessés les plus graves (6). Une chose apparait certaine: Ne plus utiliser une association HS/Dextran type RescueFlow (7).
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Impaired hemostasis frequently occurs after traumatic shock and resuscitation. The prehospital fluid administered can exacerbate subsequent bleeding and coagulopathy. Hypertonic solutions are recommended as first-line treatment of traumatic shock; however, their effects on coagulation are unclear. This study explores the impact of resuscitation with various hypertonic solutions on early coagulopathy after trauma. We conducted a prospective observational subgroup analysis of large clinical trial on out-of-hospital single-bolus (250 mL) hypertonic fluid resuscitation of hemorrhagic shock trauma patients (systolic blood pressure, e70 mmHg). Patients received 7.5% NaCl (HS), 7.5% NaCl/6% Dextran 70 (HSD), or 0.9% NaCl (normal saline [NS]) in the prehospital setting. Thirty-four patients were included: 9 HS, 8 HSD, 17 NS. Treatment with HS/HSD led to higher admission systolic blood pressure, sodium, chloride, and osmolarity, whereas lactate, base deficit, fluid requirement, and hemoglobin levels were similar in all groups. The HSD-resuscitated patients had higher admission international normalized ratio values and more hypocoagulable patients, 62% (vs. 55% HS, 47% NS; P G 0.05). Prothrombotic tissue factor was elevated in shock treated with NS but depressed in both HS and HSD groups. Fibrinolytic tissue plasminogen activator and antiYfibrinolytic plasminogen activator inhibitor type 1 were increased by shock but not thrombin-activatable fibrinolysis inhibitor. The HSD patients had the worst imbalance between procoagulation/anticoagulation and profibrinolysis/antifibrinolysis, resulting in more hypocoagulability and hyperfibrinolysis. We concluded that resuscitation with hypertonic solutions, particularly HSD, worsens hypocoagulability and hyperfibrinolysis after hemorrhagic shock in trauma through imbalances in both procoagulants and anticoagulants and both profibrinolytic and antifibrinolytic activities
24/09/2016
Transfusion en vol: Sécurité assurée
Risk Management Analysis of Air Ambulance Blood Product Administration in Combat Operations
BACKGROUND:
Between June-October 2012, 61 flight-medic-directed transfusions took place aboard U.S. Army Medical Evacuation (medevac) helicopters in Afghanistan. This represents the initial experience for pre-hospital blood product transfusion by U.S. Army flight medics.
METHODS:
We performed a retrospective review of clinical records, operating guidelines, after-action reviews, decision and information briefs, bimonthly medical conferences, and medevac-related medical records.
RESULTS:
A successful program was administered at 10 locations across Afghanistan. Adherence to protocol transfusion indications was 97%. There were 61 casualties who were transfused without any known instance of adverse reaction or local blood product wastage. Shock index (heart rate/systolic blood pressure) improved significantly en route, with a median shock index of 1.6 (IQR 1.2-2.0) pre-transfusion and 1.1 (IQR 1.0-1.5) post-transfusion (P < 0.0001). Blood resupply, training, and clinical procedures were standardized across each of the 10 areas of medevacoperations.
DISCUSSION:
Potential risks of medical complications, reverse propaganda, adherence to protocol, and diversion and/or wastage of limited resources were important considerations in the development of the pilot program. Aviation-specific risk mitigation strategies were important to ensure mission success in terms of wastage prevention, standardized operations at multiple locations, and prevention of adverse clinical outcomes. Consideration of aviation risk mitigation strategies may help enable other helicopter emergency medical systems to develop remote pre-hospital transfusion capability. This pilot program provides preliminary evidence that blood product administration by medevac is safe.
| Tags : transfusion
11/08/2016
Transfusion, Thrombosis and Bleeding Management
Special Issue: Transfusion, Thrombosis and Bleeding Management
January 2015 - Volume 70, Issue Supplement s1 - Pages 1–e41
1365-2044/asset/olbannerleft.gif?v=1&s=bd83df57543a1d11ffc15f630bb1301f0be80859)
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Blood – the most important humour? (pages 1–e1)
C. R. Bailey, A. A. Klein and B. J. Hunt
Version of Record online: 1 DEC 2014 | DOI: 10.1111/anae.12930
Review Articles
L. Green, S. Allard and R. Cardigan
☛ CPD available at http://www.learnataagbi.org
Corrected by:
Corrigendum: Modern banking, collection, compatibility testing and storage of blood and blood components
Vol. 70, Issue 3, 373, Version of Record online: 11 FEB 2015
Evidence and triggers for the transfusion of blood and blood products (pages 10–e3)
A. Shah, S. J. Stanworth and S. McKechnie
Pre-operative anaemia (pages 20–e8)
B. Clevenger and T. Richards
The pathophysiology and consequences of red blood cell storage (pages 29–e12)
D. Orlov and K. Karkouti
Red cell transfusion and the immune system (pages 38–e16)
S. Hart, C. M. Cserti-Gazdewich and S. A. McCluskey
The current place of aprotinin in the management of bleeding (pages 46–e17)
D. Royston
The current place of tranexamic acid in the management of bleeding (pages 50–e18)
B. J. Hunt
Practical management of major blood loss (pages 54–e20)
R. Gill
Management of peri-operative anti-thrombotic therapy (pages 58–e23)
J. J. van Veen and M. Makris
Laboratory monitoring of haemostasis (pages 68–e24)
A. Fowler and D. J. Perry
Point-of-care monitoring of haemostasis (pages 73–e26)
S. V. Mallett and M. Armstrong
Haemostatic management of obstetric haemorrhage (pages 78–e28)
R. E. Collis and P. W. Collins
Haemostatic management of cardiac surgical haemorrhage (pages 87–e31)
M. W. Besser, E. Ortmann and A. A. Klein
The pathogenesis of traumatic coagulopathy (pages 96–e34)
A. Cap and B. J. Hunt
Management of traumatic haemorrhage – the European perspective (pages 102–e37)
H. Schöchl, W. Voelckel and C. J. Schlimp
Management of traumatic haemorrhage – the US perspective (pages 108–e38)
R. P. Dutton
Surgery in patients with inherited bleeding disorders (pages 112–e40)
P. K. Mensah and R. Gooding
The management of abnormal haemostasis in the ICU (pages 121–e41)
A. Retter and N. A. Barrett
27/06/2016
Albumine 20% plutôt que fibrinogène ?
Influences of limited resuscitation with plasma or plasma protein solutions on hemostasis and survival of rabbits with noncompressible hemorrhage
Kheirabadi BS et Al. J Trauma Acute Care Surg. 2016;81: 42–49
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Dans ce travail et alors que l'albumine diluée n'est pas recommandée, les auteurs évoquent la possibilité que les effets favorables d'une réanimation basée sur l'apport de plasma serait lié à l'apport de protéine et en particulier d'albumine qui aurait un effet tampon élevé, réduisant l'acidose métabolique, un des facteurs de la triade létale.
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BACKGROUND:
Plasma infusion with or without red blood cells is the current military standard of care for prehospital resuscitation of combat casualties. We examined possible advantages of early and limited resuscitation with fresh plasma compared with a single plasma protein or crystalloid solutions in an uncontrolled hemorrhage model in rabbits.
METHODS:
Anesthetized spontaneously breathing rabbits (3.3 ± 0.1 kg) were instrumented and subjected to a splenic uncontrolled hemorrhage. Rabbits in shock were resuscitated at 15 minutes with Plasma-Lyte (PAL; 30 mL/kg), PAL + fibrinogen (PAL + F; 30 mL + 100 mg/kg), fresh rabbit plasma (15 mL/kg), or 25% albumin (ALB; 5 mL/kg) solution, all given in two bolus intravenous injections (15 minutes apart) to achieve a mean arterial pressure of 65 mm Hg, n = 8 to 9/group. Animals were monitored for 2 hours or until death, and blood loss was measured. Blood samples and tissues were collected and analyzed.
RESULTS:
There were no differences among groups in baseline measures and their initial bleeding volume at 15 minutes. At 60 minutes after injury, mean arterial pressure was higher with ALB than with crystalloids (PAL or PAL + F), but shock indices were not different despite the large differences in resuscitation volumes. Fibrinogen addition to PAL only increased clot strength. Plasma resuscitation increased survival rate (75%) without significant improvement in coagulation measures. Albumin administration replenished total plasma protein and increased survival rate to 100% (p < .05 vs. crystalloids). No histological adverse events were identified in the vital organs.
CONCLUSIONS:
Fibrinogen administration added to a compatible crystalloid did not improve hemostatic outcomes. Plasma resuscitation increased survival rate; however, its effects did not differ from those obtained with 25% ALB at one-third of the volume. The ALB advantage was consistent with our previous findings in which 5% ALB was used at a volume equal to plasma. The benefit of plasma for resuscitation may be mostly due to its ALB content rather than its coagulation proteins
| Tags : coagulopathie, remplissage
04/06/2016
PLyo: Une révolution ? Pas vraiment, une redécouverte
Pusateri AE et Al. Transfusion. 2016 Apr;56 Suppl 2:S128-39
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Les nouvelles modalités de transfusion mettent en avant le bénéfice de l'apport précoce de plasma. Les contraintes logistiques liées à l'emploi de plasma frais sont réelles. L'emploi de plasma lyophilisé permet de raccourcir ce délai et peut représenter dans certaines conditions d'isolement la seule source disponibles de fractions coagulantes. Le plasma lyophylisé est un vieux monsieur, mais dont la place est fondamentale. Largement utilisé notamment par l'armée française pendant la guerre d'indocchine, le SSA a maintenu sa production jusqu'à ce que l'épidémie de VIH ne survienne. Depuis les années 1980, le SSA a travaillé sans relâche pour sécuriser un produit qui retrouve la place qui lui est due dans la stratégie transfusionnelle du blessé de guerre (1) Il s'agit donc d'une redécouverte avec un emploi effectif en opération dès 1996 (2), plutôt que de révolution. Le document proposé à la lecture fait le point sur cette historique et les développements à venir. La lecture de ce document ne doit pas faire oublier la réflexion de plus en plus présente sur l'emploi en situation d'isolement de l'intérêt de la transfusion de sang total, seule source de plaquettes, associé au recours à des fractions coagulantes comme le fibrinogène et les complexes prothrombiques. Une telle association représente probablement l'avenir de la réanimation hémostatique préhospitalière (3, 4).
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Historical dried plasma development Event Selected References
1930s Plasma lyophilization developed in the 1930s.
1940—Large scale production of pooled, lyophilized plasma by both the US and British established for war time use (to meet logistical constraints of whole blood and frozen/liquid plasma).ans les années
1941—Spray dried plasma produced for the Swedish Defense Department. 21 WWII Production 20-22 British produced >500,000 U lyophilized plasma during WWII. US produced >6,000,000 U lyophilized plasma during WWII. US/British distributed world-wide. Sweden produced approximately 17,000 U spray dried plasma for Sweden and Finland.
1945—Hepatitis 23 Hepatitis as a result of plasma transfusion recognized by the end of WWII. Believed that benefits outweighed the risk.
1945-1952—Hepatitis 24 Attempts at pathogen reduction and reducing pool size not successful. Several deaths in clinical studies of ultraviolet irradiated pooled plasma.
1953
—Department of the Army (Circular 73) directed that, because of the risk of serum hepatitis, the higher cost, and the need to use it for the production of specific globulins, plasma would not be used “to support blood volume” unless dextran was not available.
—Serum albumin replaced plasma as primary resuscitative product for US Forces in Korea.
1968—National Research Council Committee on Plasma and Plasma Substitutes recommended that “the use of whole, pooled human plasma be discouraged and even discontinued unless a clear cut case can be made for its unique requirements.”
The French Military Blood Institute produced dried plasma from 1949 to 1984, and provided over 40,000 units to French military forces during the Indochina War. In 1985, production was discontinued due to risk of HIV infection.
| Tags : coagulopathie, transfusion
Acide tranexaminique systématique: La roue tournerait-elle ?
Acute Fibrinolysis Shutdown after Injury Occurs Frequently and Increases Mortality: A Multicenter Evaluation of 2,540 Severely Injured Patients
Moore HB et Al. J Am Coll Surg. 2016 Apr;222(4):347-55.
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La recommandation n°15 de la RFE Portant sur la réanimation du choc hémorragique stipule qu' il est recommandé d'administrer de l'acide tranexamique dès que possible chez les patients traumatisés à la dose de 1 g en bolus intraveineux en 10 min suivi de 1 g perfusé sur 8 h chez les patients traumatisés. Cette administration ne doit pas être initiée au delà de la 3e heure suivant la survenue d'un traumatisme avec choc hémorragique. Si l'étude CRASH-2 a montré que l'acide tranexamique réduisait significativement la mortalité. De nouvelles données disponibles depuis alimentent la discussion (1). Trois états du système de fibrinolyse peuvent être retrouvés: normal, hyperfibrinolyse, inhibition Les deux derniers sont associés à une surmortalité mais la fréquence des états d'inhibition de l'inhibition ne plaiderait pas pour une administration systématique mais ciblée d'exacyl. En qui nous concerne il faut à nouveau insister sur la précocité de l'administration d'exacyl dans l'heure chez les blessés sévères, pour lesquels le bénéfice en terme de mortalité est le plus grand (2). Une réflexion pour un emploi optimisé est en MARCHE (3, 4)
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BACKGROUND:
Fibrinolysis is a physiologic process that maintains microvascular patency by breaking down excessive fibrin clot. Hyperfibrinolysis is associated with a doubling of mortality. Fibrinolysis shutdown, an acute impairment of fibrinolysis, has been recognized as a risk factor for increased mortality. The purpose of this study was to assess the incidence and outcomes of fibrinolysis phenotypes in 2 urban trauma centers.
STUDY DESIGN:
Injured patients included in the analysis were admitted between 2010 and 2013, were 18 years of age or older, and had an Injury Severity Score (ISS) > 15. Admission fibrinolysis phenotypes were determined by the clot lysis at 30 minutes (LY30): shutdown ≤ 0.8%, physiologic 0.9% to 2.9%, and hyperfibrinolysis ≥ 3%. Logistic regression was used to adjust for age, arrival blood pressure, ISS, mechanism, and facility.
RESULTS:
There were 2,540 patients who met inclusion criteria. Median age was 39 years (interquartile range [IQR] 26 to 55 years) and median ISS was 25 (IQR 20 to 33), with a mortality rate of 21%. Fibrinolysis shutdown was the most common phenotype (46%) followed by physiologic (36%) and hyperfibrinolysis (18%). Hyperfibrinolysis was associated with the highest death rate (34%), followed by shutdown (22%), and physiologic (14%, p < 0.001). The risk of mortality remained increased for hyperfibrinolysis (odds ratio [OR] 3.3, 95% CI 2.4 to 4.6, p < 0.0001) and shutdown (OR 1.6, 95% CI 1.3 to 2.1, p = 0.0003) compared with physiologic when adjusting for age, ISS, mechanism, head injury, and blood pressure (area under the receiver operating characteristics curve 0.82, 95% CI 0.80 to 0.84).
CONCLUSIONS:
Fibrinolysis shutdown is the most common phenotype on admission and is associated with increased mortality. These data provide additional evidence of distinct phenotypes of coagulation impairment and that individualized hemostatic therapy may be required.
| Tags : coagulopathie
03/06/2016
The 2015 Remote Damage Control Resuscitation Symposium
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| Tags : transfusion, coagulopathie
01/05/2016
Albumine aussi bien que PFC ?
Influences of Limited Resuscitation with Plasma or Plasma Protein Solutions on Hemostasis and Survival of Rabbits with Non-Compressible Hemorrhage
J Trauma Acute Care Surg. 2016 Apr 27. Kheirabadi BS et Al.
BACKGROUND:
Plasma infusion with or without RBC is the current military standard of care for prehospital resuscitation of combat casualties. We examined possible advantages of early and limited resuscitation with fresh plasma compared with a single plasma protein or crystalloid solutions in an uncontrolled hemorrhage model in rabbits.
METHODS:
Anesthetized spontaneously breathing rabbits (3.3±0.1 kg) were instrumented and subjected to a splenic uncontrolled hemorrhage. Rabbits in shock were resuscitated at 15 min with Plasma-Lyte (PAL; 30 ml/kg), PAL+ fibrinogen (PAL+F; 30ml+100mg/kg), fresh rabbit plasma (PLS; 15ml/kg), or 25% albumin (ALB; 5 ml/kg) solution; all given in two bolus IV injections (15 min apart) to achieve a MAP of 65 mmHg, n=8-9/group. Animals were monitored for 2 hrs or until death and blood loss was measured. Blood samples and tissues were collected and analyzed.
RESULTS:
There were no differences among groups in baseline measures and their initial bleeding volume at 15 min. At 60 min post-injury, MAP was higher with albumin than with crystalloids (PAL or PAL+F), but shock indices were not different despite the large differences in resuscitation volumes.
Fibrinogen addition to PAL only increased clot strength. Plasma resuscitation increased survival rate (75%) without significant improvement in coagulation measures. Albumin administration replenished total plasma protein, and increased survival rate to 100% (p<.05 vs. crystalloids). No histological adverse events were identified in the vital organs.
CONCLUSION:
Fibrinogen administration added to a compatible crystalloid did not improve hemostatic outcomes. Plasma resuscitation increased survival rate, however, its effects did not differ from those obtained with 25% albumin at 1/3 of the volume. The albumin advantage was consistent with our previous findings in which 5% albumin was used at a volume equal to plasma. The benefit of plasma for resuscitation may be mostly due to its albumin content rather than its coagulation proteins
| Tags : remplissage
11/04/2016
PROPPR Study: 1-1-2 aussi bien !
Damage-control resuscitation and emergency laparotomy: Findings from the PROPPR study
Undurraga VJ et AL. J Trauma Acute Care Surg. 2016 Apr;80(4):568-75
BACKGROUND:
The Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial has demonstrated that damage-controlresuscitation, a massive transfusion strategy targeting a balanced delivery of plasma-platelet-red blood cell in a ratio of 1:1:1, results in improved survival at 3 hours and a reduction in deaths caused by exsanguination in the first 24 hours compared with a 1:1:2 ratio. In light of these findings, we hypothesized that patients receiving 1:1:1 ratio would have improved survival after emergency laparotomy.
METHODS:
Severely injured patients predicted to receive a massive transfusion admitted to 12 Level I North American trauma centers were randomized to 1:1:1 versus 1:1:2 as described in the PROPPR trial. From these patients, the subset that underwent an emergency laparotomy, defined previously in the literature as laparotomy within 90 minutes of arrival, were identified. We compared rates and timing of emergency laparotomyas well as postsurgical survival at 24 hours and 30 days.
RESULTS:
Of the 680 enrolled patients, 613 underwent a surgical procedure, 397 underwent a laparotomy, and 346 underwent an emergency laparotomy. The percentages of patients undergoing emergency laparotomy were 51.5% (174 of 338) and 50.3% (172 of 342) for 1:1:1 and 1:1:2, respectively (p = 0.20). Median time to laparotomy was 28 minutes in both treatment groups. Among patients undergoing an emergency laparotomy, the proportions of patients surviving to 24 hours and 30 days were similar between treatment arms; 24-hour survival was 86.8% (151 of 174) for 1:1:1 and 83.1% (143 of 172) for 1:1:2 (p = 0.29), and 30-day survival was 79.3% (138 of 174) for 1:1:1 and 75.0% (129 of 172) for 1:1:2 (p = 0.30).
CONCLUSION:
We found no evidence that resuscitation strategy affects whether a patient requires an emergency laparotomy, time to laparotomy, or subsequent survival.
| Tags : coagulopathie, transfusion
28/01/2016
TXA: Interrogations
Les études CRASH2 et MATTERS ont mis en évidence l'intérêt de l'emploi du TXA en traumatologie grave.
Il s'agit d'un dérivé de la lysine qui agit en se liant au plasminogène bloquant ainsi l'interaction plasminogène-fibrine, donc la fibrinolyse du caillot. Le TXA franchit la barrière sang-cerveau, diffuse dans le LCR et le globe oculaire
Persistent malgré tout quelques interrogations en matière d'innocuité persistent. Si l'étude crash2 n' pas montré de risque thromboembolique majeurs, ce n'est pas le cas d' l'étude MATTERS avec environ 10 fois plus d'épisodes thrombo-emboliques en cas d'usage de TXA. Par ailleurs il est rapporté un risque d'hypotension lors de l'administration rapide de TXA et de convulsions lors de l'emploi de posologies élevées. Ceci ne remet pas en cause le recours précoce au TXA dont l'emploi ne doit pas être banalisé et respecter un certain nombre de règles: probabilité forte de coagulopathie traumatique notamment attesté par une hypotension sévère , 1ère dose le plus tôt possible (au mieux dans la première heure) et pas après 3h, deuxième dose dans les 08h00, administration lente pour éviter hypotension, pas de surdosage facteur de crises convulsives, ne pas administrer en même temps/même ligne que du PLYO.
Un certain nombre d'études complémentaires sont en cours:
1. L'étude "Pre-hospital Antifibrinolytics for Traumatic Coagulopathy and Haemorrhage" a pour objectif d'affiner notre connaissance de l'emploi du TXA.
2.L'étude "Design of the Study of Tranexamic Acid during Air Medical Prehospital Transport (STAAMP) Trial: Addressing the Knowledge Gaps" a pour objet d'étuider la mortalité à 30 jours de traumatisés sévères pris en charge par medevac héliportées.
3. L'étude "Tranexamic Acid Mechanisms and Pharmacokinetics In Traumatic Injury (TAMPITI Trial)" vise quand à elle à confirmer un certain nombre d'hypothèses sur le mécanisme d'action.
Par ailleurs, le TXA n'est pas le seul antifibrinolyique utilisable.
| Tags : coagulopathie
21/01/2016
Le graal plaquettaire hémostatique ?
Thrombosomes: a platelet-derived hemostatic agent for control of noncompressible hemorrhage
Fitzpatrick GM et Al. Transfusion. 2013 Jan;53 Suppl 1:100S-106S
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Un thrombosome est en quelque sorte une plaquette lyophilisée dans laquelle l'eau est remplacée par un sucre particulier: le trehalose. Ré exposé à une atmosphère humide, il se réhydrate pour retrouver toutes ses propriétés. Cela ne semble pas être une simple théorie car il initierait une génération de thrombine permettant la formation d'un caillot de manière satisfaisante. Des thrombosmes, du fibrinogène et du PLyo, on peut espérer !
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BACKGROUND: Uncontrolled hemorrhage is responsible for ~80% of the potentially survivable deaths in combat and over 40% of early mortality in the under 65 age group in the United States. Providing an easily used infusible hemostatic agent to first responders could significantly reduce these fatalities. We report on an infusible lyophilized platelet-derived hemostatic agent stabilized with trehalose and polysucrose prior to and during lyophilization.
STUDY DESIGN AND METHODS: Characterization included determining the particle population size range, surface marker expression GPIb, GPIIbIIIa, and Annexin V binding. Function was assessed by aggregation, thromboelastography, and thrombin generation. Pharmacokinetics, biodistribution, and immunogenicity established using Indium111 labeled Thrombosomes in healthy New Zealand white rabbits (NZWRs), efficacy in thrombocytopenic NZWR, and safety in NZWRs, canines, and nonhuman primates.
RESULTS: Thrombosomes retained GPIIbIIIa expression (98.71% 0.18 of the rehydrated particles), a reduced expression of GPIb (47.77% 6.65), and Annexin V binding (86.05% 2.65). Aggregation to all agonists except thrombin in buffer (78.15% 2.5) was <50%. Thrombin generation and thromboelastography results demonstrated a concentration gradient that was consistent from lot to lot. There were no observed adverse events in any safety study and blood loss was reduced by >80% in the thrombocytopenic ear bleed model.
CONCLUSION: Our in vitro characterization studies in conjunction with preclinical animal safety and efficacy studies demonstrated lot consistency in manufacturing, maintenance of hemostatic functions of Thrombosomes, safety at high dose concentrations, and the potential to provide an effective hemostatic agent at the site of injury.
17/01/2016
Cyanokit pour l'hémorragie massive ?
A prospective, randomized trial of intravenous hydroxocobalamin versus whole blood transfusion compared to no treatment for class III hemorrhagic shock resuscitation in a prehospital swine model
Bebarta VS et Al. Acad Emerg Med.2015 Mar;22(3):321-30
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La prise en charge des hémorragies traumatiques en préhospitalier est basée sur la miseen oeuvre des moyens d'arrêts de ces dernières et l'initiation d'une stratégie raisonnée de remplissage vasculaire et de transfusion. L'apport équilibrée de CGR, de plasma,de fractions coagulantes et même de plaquettes fait partie de cette démarche de damage control resuscitation de même que l'apport d'acide tranexaminique pour s'opposer à une fibrinolyse précoce souvent présente. D'autres axes de recherches sont proposés. AInsi l'hydroxocobalamine, connue en tant qu'antidote de l'acide cynahydrique permettrait sur des cochons auxquels on aurait soustrait 20 ml/kg de sang de préserver la pression artérielle et la lactatémie de manière identique à celle obtenue par l'apport de sang total.
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OBJECTIVES:
The objective was to compare systolic blood pressure (sBP) over time in swine that have had 30% of their blood volume removed (Class III shock) and treated with intravenous (IV) whole blood or IV hydroxocobalamin, compared to nontreated control animals.
METHODS:
Thirty swine (45 to 55 kg) were anesthetized, intubated, and instrumented with continuous femoral and pulmonary artery pressure monitoring. Animals were hemorrhaged a total of 20 mL/kg over a 20-minute period. Five minutes after hemorrhage, animals were randomly assigned to receive 150 mg/kg IV hydroxocobalamin solubilized in 180 mL of saline, 500 mL of whole blood, or no treatment. Animals were monitored for 60 minutes thereafter. A sample size of 10 animals per group was determined based on a power of 80% and an alpha of 0.05 to detect an effect size of at least a 0.25 difference (>1 standard deviation) in mean sBP between groups. sBP values were analyzed using repeated-measures analysis of variance (RANOVA). Secondary outcome data were analyzed using repeated-measures multivariate analysis of variance (RMANOVA).
RESULTS:
There were no significant differences between hemodynamic parameters of IV hydroxocobalamin versus whole blood versus control group at baseline (MANOVA; Wilks' lambda; p = 0.868) or immediately posthemorrhage (mean sBP = 47 mm Hg vs. 41 mm Hg vs. 37 mm Hg; mean arterial pressure = 39 mm Hg vs. 28 mm Hg vs. 34 mm Hg; mean serum lactate = 1.2 mmol/L vs. 1.4 mmol/L vs. 1.4 mmol/L; MANOVA; Wilks' lambda; p = 0.348). The outcome RANOVA model detected a significant difference by time between groups (p < 0.001). Specifically, 10 minutes after treatment, treated animals showed a significant increase in mean sBP compared to nontreated animals (mean sBP = 76.3 mm Hg vs. 85.7 mm Hg vs. 51.1 mm Hg; p < 0.001). RMANOVA modeling of the secondary data detected a significant difference in mean arterial pressure, heart rate, and serum lactate (p < 0.001). Similar to sBP, 10 minutes after treatment, treated animals showed a significant increase in mean arterial pressure compared to nontreated animals (mean arterial pressure = 67.7 mm Hg vs. 61.4 mm Hg vs. 40.5 mm Hg). By 10 minutes, mean heart rate was significantly slower in treated animals compared to nontreated animals (mean heart rate = 97.3 beats/min vs. 95.2 beats/min vs. 129.5 beats/min; p < 0.05). Serum lactate, an early predictor of shock, continued to rise in the control group, whereas it did not in treated animals. Thirty minutes after treatment, serum lactate values of treated animals were significantly lower compared to nontreated animals (p < 0.05). This trend continued throughout the 60-minute observation period such that 60-minute values for lactate were 1.4 mmol/L versus 1.1 mmol/L versus 3.8 mmol/L. IV hydroxocobalamin produced a statistically significant increase in systemic vascular resistance compared to control, but not whole blood, with a concomitant decrease in cardiac output.
CONCLUSIONS:
Intravenous hydroxocobalamin was more effective than no treatment and as effective as whole blood transfusion, in reversing hypotension and inhibiting rises in serum lactate in this prehospital, controlled, Class III swine hemorrhage model.
| Tags : choc
12/01/2016
Dexamethasone: Hémostatique cérébral ?
Steroid-loaded Hemostatic Nanoparticles Alleviate Injury Progression after Blast Trauma
Hubbard WD et Al.. ACS Macro Lett., 2015, 4 (4), pp 387–391
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.
| Tags : blast, hémorragie
25/12/2015
Transfusion de CGR: Les + graves seulement
Red Blood Cell Transfusion and Mortality in Trauma Patients: Risk-Stratified Analysis of an Observational Study
Perel P et Al. PLoS Med. 2014 Jun 17;11(6):e1001664
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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).
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Background:
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.
Conclusions:
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.
| Tags : hémorragie
20/12/2015
Coagulopathie: Du fibrinogène avant tout
Trauma-induced coagulopathy: impact of the early coagulation support protocol on blood product consumption, mortality and costs
Nardi G et al. Critical Care (2015) 19:83
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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.
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INTRODUCTION:
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.
METHODS:
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.
RESULTS:
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.
CONCLUSIONS:
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.
| Tags : coagulopathie
12/11/2015
Et l'albumine ?
Is limited prehospital resuscitation with plasma more beneficial than using a synthetic colloid? An experimental study in rabbits with parenchymal bleeding
Kheirabadi BS et Al. J Trauma Acute Care Surg. 2015;78: 752-759
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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
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BACKGROUND:
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.
METHODS:
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.
RESULTS:
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).
CONCLUSION:
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
| Tags : remplissage, coagulopathie