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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



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


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 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


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



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


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


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


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


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


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


Management of bleeding & coagulopathy in major trauma: An updated European guideline


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.


Spahn DR et al. Crit Care 2013;17:R76.

Initial therapy of pelvic fractures



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25





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


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)

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29

High Plasma to RBC Ratios & Lower Mortality Rates in Trauma

Wafaisade et al, J Trauma 2011


30 Wafaisade et al, J Trauma 2011


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.


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)


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


Fixed-ratio or lab-based transfusion protocol in trauma patients

Effect of plasma transfusion on morbidity and mortality

Murad MH et al: Transfusion 2010


Murad MH et al: Transfusion 2010

Mortality in patients undergoing massive transfusion


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


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


TRALI, lung injury

Vlaar APJ and Juffermans NP: Lancet 2013


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


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


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The Use of Higher Platelet:RBC Transfusion Ratio in the Acute Phase of Trauma Resuscitation:

A Systematic Review


Method: observational studies and RCTs on higher vs. lower platelet:RBC ratios Primary outcome: mortality and morbidity

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A Systematic Review




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)


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.


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A Systematic Review


Method: observational studies and RCTs on higher vs. lower platelet:RBC ratios Primary outcome: mortality and morbidity


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