Management of the bleeding trauma patient in the ICU: A European Guideline

Rolf Rossaint

RWTH Aachen University

Financial/Professional Relationships Conflict of Interest

Lecture and consulting fees from Novo Nordisk Lecture and consulting fees from Bayer Healthcare Lecture and consulting fees and financial support for animal studies from CSL Behring Lecture and consulting fees from Air Liquide

ABC-Trauma Guideline Development

Formation of Task Force for Advanced Bleeding Care in Trauma - Cooperation with several European professional societies European Consensus Guideline Development: - Management of bleeding following major trauma A European guideline Critical Care 2007, 11:R17 Critical Care 2010, 14:R52 Professional societies enforcing the guidelines European Society for Anaesthesia (ESA) - European Society for Emergency Medicine (EuSEM) - European Trauma Society (ETS) - European Shock Society (ESS) - European Society for Intensive Care Medicine (ESICM) - European Society of Trauma and Emergency Surgery (ESTES)
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Management of bleeding following major trauma: an updated European guideline

The guideline consists of 5 parts: I. II. Initial resuscitation and prevention of further bleeding Diagnosis and monitoring bleeding

III. Rapid control of Bleeding / Surgical Interventions

IV. Resuscitation Tissue oxygenation, fluids and hypothermia

V. Management of bleeding and coagulation
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Rossaint R et al, Crit Care 14:R52, 2010

Management of bleeding following major trauma: an updated European guideline Fresh Frozen Plasma
Recommendation 24 We recommend early treatment with thawed fresh frozen plasma in patients with massive bleeding. (Grade 1B) The initial recommended dose is 10-15 ml/kg. Further doses will depend on coagulation monitoring and the amount of other blood products administered. (Grade 1C).

High Plasma to Red Blood Cell Ratios Are Associated With Lower Mortality Rates in Trauma

Wafaisade et al, J Trauma 2011

High Plasma to Red Blood Cell Ratios Are Associated With Lower Mortality Rates in Trauma

Wafaisade et al, J Trauma 2011

Management of bleeding following major trauma: an updated European guideline Platelets

Recommendation 25 We recommend that platelets be administered to maintain a platelet count above 50 109/l.(Grade 1C) We suggest maintenance of a platelet count above 100 109/l in patients with multiple trauma who are severely bleeding or have traumatic brain injury. (Grade 2C) We suggest an initial dose of 4-8 platelet concentrates or one aphaeresis pack. (Grade 2C).
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Management of bleeding following major trauma: an updated European guideline

Coagulation support for bleeding complications
Adjunctive treatment options Antifibrinolytics - tranexamic acid, -aminocaproic acid Coagulation factor substitution Fibrinogen, cryoprecipitates rFVIIa Prothrombin complex concentrate (PCC) Desmopressin AT III
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RCT on the effects of tranexamic acid in trauma patients with significant haemorrhage (CRASH-2)

1 g over 10 min followed by 1 g over 8hs

CRASH-2 trial collaborators Lancet 2010

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RCT on the effects of tranexamic acid in trauma patients with significant haemorrhage (CRASH-2)

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.
CRASH-2 trial collaborators Lancet 2010
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Management of bleeding following major trauma: an updated European guideline

Antifibrinolytic Therapy
Recommendation 27:
We suggest that antifibrinolytic agents be considered in the bleeding trauma patient. (Grade 2C 1B) We recommend monitoring of fibrinolysis in all patients and administration of antifibrinolytic agents in patients with established hyperfibrinolysis. (Grade 1B) Antifibrinolytic therapy should be guided by thrombelastometric monitoring if possible and stopped once bleeding has been adequately controlled. (Grade 2C).
Rossaint R et al. Crit Care 14:R52, 2010

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Management of bleeding following major trauma: an updated European guideline

Coagulation support for bleeding complications
Adjunctive treatment options Antifibrinolytics - tranexamic acid, -aminocaproic acid Coagulation factor substitution Fibrinogen, cryoprecipitates rFVIIa Prothrombin complex concentrate (PCC) Desmopressin AT III
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Effects of different fibrinogen concentrations on blood losss and coagulation parameters in a pig model of coagulopathy with blunt liver injury
Method: Coagulopathy in 18 anaesthetized pigs by replacing 80% of blood volume with HAES 130/0.4 and RL Randomisation: - Placebo - 70 mg/kg (F-70) fibrinogen - 200 mg/kg (F-200) fibrinogen - standardized blunt liver injury Results: fibrinogen restored coagulation dose-dependently (ROTEM) total blood loss was significantly lower in both fibrinogen groups as compared to controls (P <0.05).
Grottke et al Crit Care 2010
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FFP is independently associated with a higher risk of MOF and ARDS

Method: multicenter prospective cohort study (n=1.175)

Watson GA et al; J Trauma 67: 221230; 2009

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Management of bleeding following major trauma: an updated European guideline Fibrinogen or cryoprecipitate
Recommendation 26 We recommend treatment with fibrinogen concentrate or cryoprecipitate if significant bleeding is accompanied by a plasma fibrinogen level of less than 1.5-2.0 g/l. Grade 1C We suggest an initial fibrinogen concentrate dose of 34 g or 50 mg/kg of cryoprecipitate approximately equivalent to 1520 units in a 70 kg adult. Grade 1C

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Management of bleeding following major trauma: an updated European guideline

Coagulation support for bleeding complications
Adjunctive treatment options Antifibrinolytics - tranexamic acid, -aminocaproic acid Coagulation factor substitution Fibrinogen, cryoprecipitates rFVIIa Prothrombin complex concentrate (PCC) Desmopressin AT III Rossaint R et al. Crit Care 14:R52, 2010

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30d Incidence of MOF, ARDS and death ITT-population

BLUNT Trauma
40 35 30 Incidence (%) 25 20 15 10 5 0
n=9 n=5 n=3 n=22

PENETRATING Trauma
30 25 Incidence (%) 20 15
n=7 n=18 n=17

p=0.03
n=12

n=17

10 5 0
n=2

n=5 n=4

MOF

ARDS

Death

Placebo rFVIIa

MOF

ARDS

Death

Boffard KD et al. J Trauma 2005; 59:8-18

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Efficacy and Safety of rFVIIa in the Management of Refractory Traumatic Hemorrhage: The CONTROL Trial

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Efficacy and Safety of rFVIIa in the Management of Refractory Traumatic Hemorrhage: The CONTROL Trial
Clinical Outcomes (30-d ITT Analysis)

Conclusions: rFVIIa reduced blood product use but did not affect mortality compared with placebo.
Hauser CJ et al. J Trauma 69: 489500, 2010
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Safety of Recombinant Activated Factor VII in 35 Randomized Clinical Trials

Conclusion: The risk-benefit considerations should be evaluated before administering any hemostatic agent.
Levy et al; NEJM363:1791-800 2010
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Management of bleeding following major trauma: an updated European guideline

Recommendation 28

We suggest that the use of rFVIIa be considered if major bleeding in blunt trauma persists despite standard attempts to control bleeding and best practice use of blood components. Grade 2C

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Management of bleeding following major trauma: an updated European guideline

Coagulation support for bleeding complications
Adjunctive treatment options Antifibrinolytics - tranexamic acid, -aminocaproic acid Coagulation factor substitution Fibrinogen, cryoprecipitates rFVIIa Prothrombin complex concentrate (PCC) Desmopressin AT III Rossaint R et al. Crit Care 14:R52, 2010

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Management of bleeding following major trauma: an updated European guideline Prothrombin complex concentrate (PCC)
Recommendation 29

We recommend the use of prothrombin complex concentrate only for the emergency reversal of vitamin K-dependent oral anticoagulants.

Grade 1B

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Retrospective analysis of patients receiving >5 RBC/24 hours

N = 131

119 only CFC

CFC: coagulation factor concentrates

12 CFC + FFP (in the ICU)

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Individualised goal directed coagulation therapy using ROTEM and coagulation factor concentrates
Haemostatic therapy and RBC transfusion

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Individualised Goal directed coagulation therapy using ROTEM and coagulation factor concentrates
Comparison of the observed mortality with the mortality predicted by the trauma injury severity score (TRISS) and by the revised injury severity classification (RISC) score

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Key goals for the management of treating the bleeding trauma patient
1. 2. 3. 4. Achieve normothermia 8 Steps to support coagulation Achieve normal pH Achieve normal Ca++ Treat with FFP, if PT or aPTT abnormal Crystalloids 9 Treat with platelets, if < 100 x 10 Colloids Treat with fibrinogen, if < 1,5-2.0g/l Treat with antifibrinolytics RBC Hct ? 2124% (always if hyperfibrinolysis is present) PT, aPTT> 1.5x normal FFP/PCC Treat with rFVIIa, if all else fails: Platelets > 50 x 109 Fg Fg ? 1.0 g -1 2.0 l Fibrinogen > 1 g/l Hct > 24 9 Plt < 50x10 l-9 100x101 Plt pH > 7.2
0

5. 6. 7.
8.

0.5

1.0

1.5

2.0

2.5

Blood Volume Replacement

figure modified from Spahn DR and Rossaint R. Br J Anaesth 2005; 95:130

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