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Klinik für Operative Intensivmedizin und Intermediate Care
Klinik für Operative Intensivmedizin und Intermediate Care
Klinik für Operative Intensivmedizin und Intermediate Care
Keine Zeit zum Taktieren: Massentransfusion im
Schockraum Univ.-Prof. Dr. med. Gernot Marx, FRCA
Conflict of Interest
Koordinator S3 LL Volumentherapie BBraun Melsungen AG Edwards Life Science Philips CLS Behring Linde Gase Orion Pharma Gambro Thermo Fisher Jena Analytik Fresenius EU NRW-Ziel2 DFG BMBF Intramural faculty grants DFG-Exzellenzinitiative
Klinik für Operative Intensivmedizin und Intermediate Care
Klinik für Operative Intensivmedizin und Intermediate Care
103 Intensivbetten - 75 Beatmungsbetten,
- 6 Betten für Schwerbrandverletzte - 18 Weaning Betten - Tele-ICU
- 28 IMC Betten 16 Oberärzte, 55 Fach- und Assistenzärzte, 350 Pflegekräfte ca. 5.000 Patienten/Jahr Schwerpunkte: - Sepsis - ARDS/ECMO - Verbrennungsintensivmedizin - Weaning - Telemedizin
Klinik für Operative Intensivmedizin und Intermediate Care
Bleeding is the main cause of mortality
40% 51%
4% 1% 4%
CNS + Exsanguination Organ failure Others
Sauaia, J Trauma 1995;38:185-93
Patients dying within 48 h in the hospital (n = 154, 37±1.2 years)
Exsanguination
CNS
Traumatic coagulopathy
Lethal triad - Hypothermia - Acidosis - Coagulopathy
Ferrara A et al. Am J Surg 1990; 160: 515
If this lethal triad is present…surgical control of bleeding alone is unlikely to be successful
Klinik für Operative Intensivmedizin und Intermediate Care
Klinik für Operative Intensivmedizin und Intermediate Care Hypothermia
Strong relationship between temperature and survival - <32°C following injury is going along with a nearly 100%
mortality rate - Association or cause?
Mild hypothermia - platelet function reduced Severe hypothermia - reduced function of the clotting
factors Clotting tests performed at 37°C do not reflect the state
of the patient, and may therefore be misleading
Klinik für Operative Intensivmedizin und Intermediate Care Acidosis
Marker of inadequate tissue utilisation of oxygen Duration of severe hypotension related to abnormal
coagulation Duration of acidosis related to coagulation abnormality
Treated by improving tissue oxygen delivery
Klinik für Operative Intensivmedizin und Intermediate Care
Development of Traumatic Coagulopathy
Haemorrhagic shock
Haemodilution
Consumption of clotting factors
Bleeding
Fibrinolysis
Hypothermia
Acidosis
Klinik für Operative Intensivmedizin und Intermediate Care Loss of Clotting Factors
Bleeding causes loss of coagulation factors Loss proportional to grade of shock
Coagulation affected once factors are below 25% of
normal level Believed to be a minor problem until intravenous fluid
treatment started
Klinik für Operative Intensivmedizin und Intermediate Care Dilution of Clotting Factors
Resuscitation fluids Transfused packed cells are plasma poor
Factor replacement (Fibrinogen, Fresh Frozen Plasma
etc.) often given late
Can one make a non-lethal injury lethal by over-resuscitating?
How Much Fluid?
Traditional resuscitation guidelines: Early + aggressive fluid administration to restore blood
pressure and tissue oxygenation as soon as possible Problems:
- Increased hydrostatic pressure on the wound - Dislodgement of blood clots - Dilution of coagulating factors - Cooling of the patient
Klinik für Operative Intensivmedizin und Intermediate Care
Klinik für Operative Intensivmedizin und Intermediate Care
Acute Traumatic Coagulopathy Initiated by Hypoperfusion
Brohi K et al. Ann Surg 2007;245: 812–818
Effects of tissue hypoperfusion on coagulation in a prospective cohort study of 210 patients
Klinik für Operative Intensivmedizin und Intermediate Care
Early traumatic coagulopathy occurs only in the presence of tissue hypoperfusion and appears to occur
without significant consumption of coagulation factors.
Brohi K et al. Ann Surg 2007;245: 812–818
Effects of tissue hypoperfusion on coagulation
Acute Traumatic Coagulopathy Initiated by Hypoperfusion
Klinik für Operative Intensivmedizin und Intermediate Care
Modified from Lier et al Anaesthesist 2009
Hypoperfusion / Shock
Endothelium injury increases thrombomudulin liberation
C
is
Fibrin splitt products
Consumption of PAI 1 activation
Systemic anticoagulation
inhibition
Hyperfibrinolysis
Coagulopathy of Trauma: A Review of Mechanisms
Klinik für Operative Intensivmedizin und Intermediate Care Role of fibrinogen in TIC
Fries and Martini:BJA 105 (2): 116–21 (2010)
Changes in fibrinogen synthesis and breakdown in pigs after haemorrhage, hypothermia, and acidosis
Klinik für Operative Intensivmedizin und Intermediate Care
Consumption of Clotting Factors
Massive tissue factor exposure gives intense early (pre-hospital) thrombosis Thrombosis and fibrinolysis both increased, consuming
clotting factors Clot formation delayed (prothrombin time)
Clot quality impaired
Klinik für Operative Intensivmedizin und Intermediate Care
The lethal sixpack
Main factors for Trauma induced coagulopathy: 1. Tissue injury 2. Hypothermia 3. Acidosis 4. Dilution 5. Shock 6. Inflammation.
Hess JR et al J Trauma 2008
Klinik für Operative Intensivmedizin und Intermediate Care
Incidence of trauma induced coagulopathy
Brohi et al. Curr Opin Crit Care 13:680–685, 2007
Coagulation parameters at admission fo trauma patients:
TIC occured in ~ 25 % and was associated with a 3-4-fold higher mortality.
Lier et al Anaesthesist 2009
High-pressure Resuscitation from Hemorrhagic Shock
Blood loss
Hypotension
High pressure level
Increased hemorrhage volume
Vasopressors Fluids
Klinik für Operative Intensivmedizin und Intermediate Care
Management of bleeding & coagulopathy in major trauma: An updated European guideline
Klinik für Operative Intensivmedizin und Intermediate Care
Rossaint R et al. Crit Care 2016;20: 100
Early abdominal bleeding control
Grade 1C
We recommend that early bleeding control of the abdomen be achieved using packing, direct surgical bleeding control and the use of local haemostatic procedures. In the exsanguinating patient, aortic cross-clamping may be employed as an adjunct.
Klinik für Operative Intensivmedizin und Intermediate Care
Spahn DR et al. Crit Care 2013;17:R76.
Initial therapy of pelvic fractures
Rossaint R et al. Crit Care 2016;20: 100
Klinik für Operative Intensivmedizin und Intermediate Care
24
Klinik für Operative Intensivmedizin und Intermediate Care
Rossaint R et al. Crit Care 2016;20: 100
Management of bleeding & coagulopathy in major trauma: An updated European guideline
25
Klinik für Operative Intensivmedizin und Intermediate Care
Rossaint R et al. Crit Care 2016;20: 100
Management of bleeding & coagulopathy in major trauma: An updated European guideline
Klinik für Operative Intensivmedizin und Intermediate Care
Effects of tranexamic acid in bleeding trauma patients (CRASH-2)
CRASH-2 trial collaborators Lancet 2010
1 g over 10 min followed by 1 g over 8hs
Nurse, tranexamic acid
Klinik für Operative Intensivmedizin und Intermediate Care
CRASH-2 trial collaborators Lancet 2010
Conclusion: Tranexamic acid reduced the risk of death in bleeding trauma patients in this study. On the basis of these results,tranexamic acid should be considered for use in bleeding trauma patients.
Effects of tranexamic acid in bleeding trauma patients (CRASH-2)
28
Klinik für Operative Intensivmedizin und Intermediate Care
Rossaint R et al. Crit Care 2016;20: 100
Management of bleeding & coagulopathy in major trauma: An updated European guideline
29
High Plasma to RBC Ratios & Lower Mortality Rates in Trauma
Wafaisade et al, J Trauma 2011
Klinik für Operative Intensivmedizin und Intermediate Care
30 Wafaisade et al, J Trauma 2011
Klinik für Operative Intensivmedizin und Intermediate Care
High Plasma to RBC Ratios & Lower Mortality Rates in Trauma
31 Sambasivan CN et al; J Trauma. 2011;71: S329–S336
High Ratios of Plasma & Platelets to RBC Do Not Affect Mortality
Method: Records of 1,788 trauma patients who received < 10 PRBC in 24 hrs at 23 United States Level I trauma centers were reviewed.
Conclusions: A high ratio of FFP:PRBC and PLT:PRBC was associated with fewer ICU-free days and fewer ventilator-free days.
Klinik für Operative Intensivmedizin und Intermediate Care
Fixed-ratio or lab-based transfusion protocol in trauma patients
Nascimento B. et al. CMAJ (2013) doi:10.1503/cmaj.121986
Method: • hypotonic and bleeding trauma pts. with expected massive
transfusion (≥ 10 RBC/24h) • Randomisation: fixed-ratio (1:1:1) transfusion protocol (n=40) or
laboratory-results–guided transfusion protocol (control; n=38)
Klinik für Operative Intensivmedizin und Intermediate Care
PRT (n = 78) 28 day mortality in ITT population 32% (1:1:1) vs. 14% (control) RR 2.27 (CI 0.98 – 9.63)
Nascimento B. et al. CMAJ (2013) doi:10.1503/cmaj.121986
Klinik für Operative Intensivmedizin und Intermediate Care
Fixed-ratio or lab-based transfusion protocol in trauma patients
Effect of plasma transfusion on morbidity and mortality
Murad MH et al: Transfusion 2010
Klinik für Operative Intensivmedizin und Intermediate Care
Murad MH et al: Transfusion 2010
Mortality in patients undergoing massive transfusion
Klinik für Operative Intensivmedizin und Intermediate Care
Effect of plasma transfusion on morbidity and mortality
Higher Platelet:RBC Transfusion Ratio in the Acute Phase of Trauma Resuscitation:
Hallet J et al: Crit Care Med 2013; 41:2800–2811
Klinik für Operative Intensivmedizin und Intermediate Care
Transfusion-related acute lung injury
Vlaar APJ and Juffermans NP: Lancet 2013
All blood products can induce antibody-mediated TRALI if the antibody is strong enough and the patient has susceptible risk factors, even red blood cells containing only10–20 mL of plasma
Klinik für Operative Intensivmedizin und Intermediate Care
TRALI, lung injury
Vlaar APJ and Juffermans NP: Lancet 2013
Klinik für Operative Intensivmedizin und Intermediate Care
Lindgren L. et al. Acta Anaesthesiol Scand (1996) 40: 641 Silliman C. C. et al. Blood (2005) 105: 2266 Toy P. et al. Crit Care Med (2005) 33: 721 Rana R. et al. Transfusion (2006) 46: 1478 Eder A. F. et al. Transfusion (2007) 47: 599
Chaiwat O. et al. Anesthesiology (2009) 110: 351
Klinik für Operative Intensivmedizin und Intermediate Care
TRALI, lung injury
Klinik für Operative Intensivmedizin und Intermediate Care Take home messages
Pelvic fracture & abdominal injury - Early stabilisation - Early bleeding control
Main factors for Trauma induced coagulopathy: Tissue injury, Hypothermia, Acidosis, Dilution, Shock, Inflammation Resuscitation - Fluids - RBC/FFP according to laboratory values Awareness for Coagulopathy
Massivtransfusion im Schockraum
www.operative-intensivmedizin.de
Klinik für Operative Intensivmedizin und Intermediate Care
42
The Use of Higher Platelet:RBC Transfusion Ratio in the Acute Phase of Trauma Resuscitation:
A Systematic Review
Hallet J et al: Crit Care Med 2013; 41:2800–2811
Method: observational studies and RCTs on higher vs. lower platelet:RBC ratios Primary outcome: mortality and morbidity
43
The Use of Higher Platelet:RBC Transfusion Ratio in the Acute Phase of Trauma Resuscitation:
A Systematic Review
Hallet J et al: Crit Care Med 2013; 41:2800–2811
Klinik für Operative Intensivmedizin und Intermediate Care
Klinik für Operative Intensivmedizin und Intermediate Care
Estimation of fibrinogen levels on ER admission
Schlimp et al. Critical Care 2013, 17:R137
45
FFP is independently associated with a higher risk of MOF and ARDS
Watson GA et al; J Trauma 67: 221–230; 2009
Method: multicenter prospective cohort study (n=1.175)
Klinik für Operative Intensivmedizin und Intermediate Care
V. Management of bleeding and coagulation Fibrinogen: R 27
R24 Antifibrinolytic agents
*** Tranexamic acid should be administered as
early as possible to the trauma patient who is bleeding or at risk of significant haemorrhage at
a loading dose of 1 g infused over 10 min, followed by an intravenous infusion of 1 g over 8h. Tranexamic acid should be administered to
the bleeding trauma patient within 3 h after injury. Protocols for the management of
bleeding patients may consider administration of the first dose of tranexamic acid en route to
the hospital.
R27 Fibrinogen & cryoprecipitate
*** Fibrinogen concentrate or cryoprecipitate should
be administered if significant bleeding is accompanied by thromboelastometric signs of a
functional fibrinogen deficit or a plasma fibrinogen level of less than 1.5-2.0 g/l; an initial
fibrinogen dose of 3-4 g or 50 mg/kg of cryoprecipitate, approximately equivalent to 15-20 single donor units in a 70 kg adult, may be
employed. Repeat doses may be guided by viscoelastic monitoring and laboratory
assessment of fibrinogen levels.
R26 Plasma
*** Plasma or fibrinogen should be administered initially in patients with massive bleeding. If further plasma is administered, an optimal
plasma:red blood cell ratio may be at least 1:2. Plasma transfusion should be avoided in
patients without substantial bleeding.
R25 Calcium
*** Ionised calcium levels should be monitored and
maintained within the normal range during massive transfusion.
R23 Coagulation support
*** Monitoring and measures to support
coagulation should be initiated as early as possible.
V. Management of bleeding and coagulation
R28 Platelets
*** Platelets should be administered to maintain a platelet count above 50×109/l. A platelet count
above 100×109/l in patients with ongoing bleeding and/or traumatic brain injury may be
maintained. An initial dose of 4-8 platelet concentrates or one aphaeresis pack may be
used.
Klinik für Operative Intensivmedizin und Intermediate Care
47
The Use of Higher Platelet:RBC Transfusion Ratio in the Acute Phase of Trauma Resuscitation:
A Systematic Review
Hallet J et al: Crit Care Med 2013; 41:2800–2811
Method: observational studies and RCTs on higher vs. lower platelet:RBC ratios Primary outcome: mortality and morbidity
Klinik für Operative Intensivmedizin und Intermediate Care