Gerinnungsmanagement schon präklinisch?

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1 Klinik für Anästhesiologie und Operative Intensivmedizin Gerinnungsmanagement schon präklinisch? Symposium Entwicklungen in der Notfallmedizin 15. Kongress der DIVI Leipzig, 02. Dezember 2015 Heiko Lier

2 Interessenskonflikte? Vortragshonorare, Reisekostenerstattungen o.ä. erhielt ich von: DRK-Blutspendedienst West CSL Behring Ferring Mitsubishi Pharma NovoNordisk Tem International Folie 2

3 Laktat bewirkt linearen Ca i ++ Vivien B et al. Crit Care Med 2005 Rahmenbedingungen der Gerinnung Lier H et al. Anästhesist 2007 Lier H et al. J Trauma 2008 Prophylaxe & Therapie!! möglichst vermeiden: Temperatur 34 C (Ziel: Normothermie) ESA 2013: 1B (strong recommendation, moderate quality evidence) (Rec ) ph 7,1 bzw. 7,2 ESA 2013: 1C (strong recommendation, low-quality or very low quality quality evidence) (Rec ) ionisiertes Kalzium 0,9 mmol/l (Ziel: Normokalzämie) ESA 2013: 2B (weak recommendation, moderate quality evidence) (Rec ) Hämatokrit 21% Kombination wirkt zumindest additiv hypotherm und azidotisch sehr kritisch Folie 3

4 externe Blutstillung Celox gauze dressing C.A.T. Combat Application Tourniquet QuickClot gauze Folie 4

5 Trauma und Laborwerte? Point of care coagulometry in prehospital emergency care: an observational study Beynon C et al. Scand J Trauma Resusc Emerg Med ; 103 Notfallpatienten; Alarmierungsgrund: cardiovascular (n = 39), Trauma (n = 19), Neurologie (n = 16), Atmung (n = 9), andere (n = 20). CoaguCheck XS (Roche Diagnostics, Mannheim) bei INR >1,3: Sensitivität 100%, Spezifität 98,7% medianer Zeitgewinn: 69 min There is actually no sound evidence from well designed studies that confirm the usefulness of SLTs for diagnosis of coagulopathy or to guide haemostatic therapy. Haas T et al. Br J Anaesth 2015 Folie 5

6 Trauma und Volumenersatz? Pre-Hospital Resuscitation of Traumatic Hemorrhagic Shock with Hypertonic Solutions Worsen Hypo-Coagulation and Hyper-Fibrinolysis Delano ML et al. Shock 2015 prospective observational study as an a priori subgroup analysis of a previously published, multicenter, randomized, controlled, double-blind, 3-arm clinical trial; single bolus (250 ml); 0.9% NaCl (NS) versus 7.5% hypertonic saline, alone or combined with 6% Dextran 70 We concluded that resuscitation with hypertonic solutions, particularly 7.5% NaCl ± 6% dextran, worsen hypocoagulability and hyperfibrinolysis following hemorrhagic shock in trauma through imbalances in both pro- and anticoagulants, and both pro- and anti-fibrinolytic activities. Folie 6

7 Militär more than 90% of potentially survivable casualties die from hemorrhage TxA: 1g by combat medic US Army PTC RBC: a 37% reduction in 30-day mortality for casualties with an injury severity score (ISS) of more than 15 when compared with conventional; 15% of patients overall received PH RBC transfusion, and among those with ISS of more than 15, a third of casualties received PH RBC transfusion. Morrison JJ et al. Ann Surg 2013 Folie 7

8 Gibt es zivile Daten? Massive transfusion policies at trauma centers participating in the American College of Surgeons Trauma Quality Improvement Program. Camazine MN et al. J Trauma Acute Care Surg Elektronische Umfrage bei 132 ACS-TQIP Zentren Folie 8

9 Tranexamsäure präklinisch? 3. European Trauma Guidelines: Recom. 24 We suggest that protocols for the management of bleeding patients consider administration of the first dose of tranexamic acid en route to the hospital. 2C (weak recommendation, low-quality or very low-quality evidence) Spahn D et al. Crit Care Auflage S3-LL Polytrauma / Schwerverletztenversorgung : Empfehlung 13 Bei massiv-blutenden Patienten kann die prähospitale Gabe von TxA sinnvoll sein. GoR 0 AWMF 2016 Basis: CRASH-2 follow-up CRASH-2 trial collaborators. Lancet 2011 Folie 9

10 CRASH-2 Ergebnisse The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial CRASH-2 trial collaborators. Lancet 2011 TxA should be given as early as possible : am Besten innerhalb von 1 Std. (dann death due to bleeding 32%), spätestens nach 3 Stunden Folie 10

11 CRASH-2 Kritikpunkte keine Messung von Gerinnnungs- (Fibrinolyse-) parametern im Labor Gerinnungsstudie? größtenteils (>95%) Krankenhäuser in Entwicklungs- / Schwellenländern Übertragbarkeit auf Industrienationen? Reduktion der Sterblichkeit von 16 auf 14,5%, d.h. absolute Reduktion der Sterblichkeit um 1,5% bei Patienten overpowered? 50,4% Bluttransfusion: Mittelwert 6,06 (±9,98) aber Median 3 (2-6) EK Massivtransfusion? keine Blutprodukte in der TxA-Gruppe eingespart (TxA 50,4% vs. NaCl 51,3%, nicht signifikant) Pat., Verstorbene (15,3%), blutungsbedingte Tote (TxA: 489 = 4,9% vs. NaCl: 574 = 5,7%; p = 0,0077) ausreichend für Analyse? Patienten aber nur 369 thrombembolische Komplikationen (Myokardinfarkt, Schlaganfall, Lungenembolie, tiefe Venenthrombose) (TxA: 168 = 1,7% vs. NaCl: 201 = 2,0%; n.s. und TVT: 0,4%) 1.) Unglaublich wenig (TVT bei Hochrisiko-Pat %, etwa 3% aller TVT bei Polytraumata erleiden eine LE Holley AD et al. Curr Opin Crit Care 2013). 2.) Ist NaCl thrombogen? Folie 11

12 Tranexamsäure Wirksamkeit Lancet vs Patienten NNT = 67 absolute mortality risk reduction = 1,5% Arch Surg / 896 Patienten NNT = 15 absolute mortality risk reduction = 6,5% Bei Massivtransfusion: NNT = 7 absolute mortality risk reduction = 13,7% Folie 12

13 Tranexamsäure Implementierte Anwendung von TxA im zivilen Notarztbereich: England: NHS ambulance service seit Juni 2011 Norwegen: Bergen Air ambulance seit 2011 Israel: national EMS system seit 2012 Kanada: British Columbia Ambulance Service s (BCAS) AirEvac and Critical Care Operations seit 2011 Folie 13

14 Tranexamsäure Tranexamic acid in the prehospital setting: Israel Defense Forces initial experience Lipsky AM et al. Injury 2014 Dez 2011 bis Feb 2013; 40 mal prähospitale Gabe von TxA; zivil und militärisch; 55% penetrierende Verletzung; mediane Zeit zwischen Verletzung und TxA 46 min (IQR: 40-66) 1. Any penetrating injury to the torso, including the neck, axillae, groin, and buttocks. 2. Blunt or penetrating injury accompanied by signs of shock. Shock was defined as the presence of any of the following: systolic blood pressure (SBP) <90 mmhg, heart rate (HR) >100 beats per minute on repeated measurement, delayed capillary refill (>2 s), or altered level of consciousness in a casualty without blunt head trauma. This definition of shock was chosen to be consistent with the IDF fluid resuscitation protocol for trauma. If shock is diagnosed, TXA is given even if haemorrhage has ceased., there is likely benefit in the civilian sector as well. The safety profile of TXA is an important consideration as prehospital personnel tended to overtreat casualties without indications for TXA per protocol. Folie 14

15 Erythrozytenkonzentrate Pretrauma Center Red Blood Cell Transfusion Is Associated With Reduced Mortality and Coagulopathy in Severely Injured Patients With Blunt Trauma Brown JB et al. Ann Surg 2015 Data analysis of multicenter prospective cohort study ( ; blunt injured patients in shock arriving at a trauma center within 2 hours of injury (mean 60 min); 1415 subjects, 50 received PTC RBC transfusion; median 1.3 U of PTC RBC; 113 matched-pairs (matched-pairs:) PTC RBC transfusion was associated with a 98% reduction in odds of 24-hour mortality (OR = 0.02; 95% CI, ; P = 0.04), 88% reduction in the risk of 30-day mortality (hazard ratio = 0.12; 95% CI, ; P = 0.01), and 99% reduction in odds of TIC (OR = 0.01; 95% CI, ; P = 0.05)... Folie 15

16 Erythrozytenkonzentrate Pre-Trauma Center Red Blood Cell Transfusion Is Associated with Improved Early Outcomes in Air Medical Trauma Patients Brown JB et al. Am Coll Surg 2015 retrospective cohort study; ; matched pair analysis 240 pat with PTC vs. 480 control; PTC RBC was also associated with increased odds of 24-hour survival (AOR = 6.31; 95% CI, ; p < 0.01), lower odds of shock (AOR = 0.24; 95% CI, ; p ¼ 0.02), and lower 24-hour RBC requirement (Coefficient -4.5 RBC units; 95% CI, -8.3 to -0.7; p = 0.02). Pre-trauma center RBC appears beneficial in severely injured air medical trauma patients and prospective study is warranted as PTC RBC transfusion becomes more readily available. Folie 16

17 Plasma Prehospital use of plasma: the blood bankers' perspective. Hewrvig T et al. Shock THOR (Trauma Hemostasis and Oxygenation Research Network) Meeting, Bergen 2013; Available evidence indicates that prehospital use of plasma may improve remote damage control resuscitation, although level I evidence is lacking.... There are few, if any, clinical contraindications to the prehospital use of plasma, except for blood group incompatibility and the danger of transfusion-induced acute lung injury, which can be circumvented in various ways.... Prehospital use of plasma should occur within the framework of clinical algorithms and prospective clinical studies. now is the time for both military and civilian transfusion systems to prepare for prehospital use of plasma in massively bleeding casualties. Folie 17

18 Freeze dried plasma and fresh red blood cells for civilian clinical significant hemorrhage on scene ± systolic blood pressure less than 90 mmhg ± minimal response to initial fluid resuscitation blunt trauma (31%), penetrating trauma (25%), nontrauma (44%) LyoPlas ( ensures both coagulation factors and volume replacement, 200 ml = 2 U): 16 Pat.; 75% received TxA RBC: 4 Pat. prehospital hemorrhagic shock resuscitation Sunde GA et al. J Trauma Acute Care Surg 2015 Norway; retrospective observational study; civilian Helicopter Emergency Medical Service (experienced anaesthesiologist); LyoPlas N-w (AB) May May 2014; RBC (0Rh (D) negative) since May 2014; plasma first transfusion policy no side effects / transfusion-related complications only 19% prehospital crystalloids (median 0 ml) 2 deaths on scene, 14 survivors for 30 days Our small study indicates that introduction of FDP into civilian HEMS seems feasible and may be safe and that logistical and safety issues for implementing RBCs are solvable. Erythrozytenkonzentrate und Plasma Folie 18

19 Alles Practical translation of hemorrhage control techniques to the civilian trauma scene. Lockey DJ et al. Transfusion 2013 London s Air Ambulance; urban physician-led (experienced emergency physicians or anesthesiologists) prehospital trauma service; 5-6 trauma patients per day; 20% penetrating trauma; pre-hospital hemorrhage care bundle TxA patients suspected of major hemorrhage gentle patient handling external hemorrhage control: Combat Application Tourniquet, Celox gauze dressing since 2012: 4 U 0 neg. RBC given on scene in approximately 4% of trauma mission no prehospital FFP Folie 19

20 Aktuelle Studien (Auswahl) PATCH (Pre-hospital Antifibrinolytics for Traumatic Coagulopathy and Haemorrhage study) Gruen RL et al. Med J Aust 2013 STAAMP (Study of Tranexamic Acid during Air Medical Prehospital Transport) Brown JB et al. Prehosp Emerg Care 2014 FlinTIC (Fibrinogen in Trauma-Induced Coagulopathy) Maegele M et al. J Trauma Acute Care Surg 2015 PROSPERO (Protocol for a systematic review of the clinical effectiveness of prehospital blood components compared to other resuscitative fluids in patients with major traumatic haemorrhage) Brown JB et al. System Reviews 2014 PUPTH (Prehospital use of plasma in traumatic hemorrhage (The PUPTH Trial)) Reynolds PS et al. Trials 2015 PAMPER (Prehospital air medical plasma (PAMPer) trial) Brown JB et al. Prehosp Emerg Care 2015 Folie 20

21 Zusammenfassung: Prähospitale Gerinnungstherapie Warmhalten / Erwärmen sinnvoll Tourniquets / Blutung stillende Verbände Tranexamsäure (TxA) (vermutlich) sinnvoll - ggf. Kosten-/ Nutzenanalyse des Notarzteinsatzspektrums (vermutlich) sinnvoll - kostengünstig - 1 g langsam iv., ggf. 1 g über 8h - bei massiver / lebensbedrohlicher Blutung (durch Hyperfibrinolyse) Blutprodukte Erythrozytenkonzentrate (getrocknetes) Plasma - Kosten-/ Nutzenanalyse des Notarzteinsatzspektrums - bei hämorrhagischem Schock - bei penetrierendem Trauma des Torso (vermutlich) sinnvoll - Logistik (Blutbank; frisches Blut; täglicher Austausch; Gefriertasche mit Temperaturanzeige) - Vorschlag: 4 EK 0 neg. (vermutlich) sinnvoll - Plasma als Volumenersatz anstatt Kristalloide Faktorenkonzentrate (bisher) nicht sinnvoll Folie 21

22 Vielen Dank! Hemostasis = Love Everybody talks about it, nobody understands it. JH Levy heiko.lier@uk-koeln.de Folie 22