The European guideline on management of major bleeding and coagulopathy following trauma: fifth edition

Answer 1

I. Initial resuscitation and prevention of further bleeding Minimal elapsed time

Question 2

What is the recommended management of local bleeding?

Answer 2

We recommend local compression to limit life-threatening bleeding. (Grade 1A) We recommend adjunct tourniquet use to stop life-threatening bleeding from open extremity injuries in the pre-surgical setting. (Grade 1B) Werecommend the adjunct use of a pelvic binder to limit life-threatening bleeding in the presence of a suspected pelvic fracture in the pre-surgical setting. (Grade 1B)

Question 3

What ventilation strategies are recommended for use in poly trauma patients?

Answer 3

We recommend the avoidance of hypoxaemia. (Grade 1A)
We recommend normoventilation of trauma patients. (Grade 1B)
We suggest hyperventilation in the presence of signs of imminent cerebral herniation. (Grade 2C)

Question 4

Initial assessment

Answer 4

We recommend that the physician clinically assess the extent of traumatic haemorrhage using a combination of patient physiology, anatomical injury pattern, mechanism of injury and the patient response to initial resuscitation. (Grade 1C)
We suggest that the shock index (SI) be used to assess the degree of hypovolaemic shock. (Grade 2C)

Question 5

Immediate intervention

Answer 5

Recommendation 5 We recommend that patients with an obvious bleeding source and those presenting with haemorrhagic shock in extremis and a suspected source of bleeding undergo an immediate bleeding control procedure. (Grade 1C)

Question 6

Further investigation

Answer 6

Recommendation 6 We recommend that patients without a need for immediate bleeding control and an unidentified source of bleeding undergo immediate further investigation. (Grade 1C)

Question 7

Imaging

Answer 7

Recommendation 7 We recommend the use of focused assessment with sonography in trauma (FAST) ultrasound for the detection of free fluid in patients with torso trauma. (Grade 1C) We recommend early imaging using contrast-enhanced whole-body CT (WBCT) for the detection and identification of type of injury and potential source of bleeding. (Grade 1B)

Question 8

Haemoglobin

Answer 8

Recommendation 8 We recommend that a low initial Hb be considered an indicator for severe bleeding associated with coagulopathy. (Grade 1B) We recommend the use of repeated Hb measurements as a laboratory marker for bleeding, as an initial Hb value in the normal range may mask bleeding. (Grade 1B)

Question 9

Serum lactate and base deficit

Answer 9

We recommend serum lactate and/ or base deficit measurements as a sensitive test to estimate and monitor the extent of bleeding and shock. (Grade 1B)

Question 10

Coagulation monitoring

Answer 10

Recommendation 10 We recommend that routine practice include the early and repeated monitoring of haemostasis, using either a combined traditional laboratory determination [prothrombin time (PT), platelet counts and Clauss fibrinogen level] and/or point-of-care (POC) PT/international normalised ratio (INR) and/or a viscoelastic method (VEM). (Grade 1C) We recommend laboratory screening of patients treated or suspected of being treated with anticoagulant agents. (Grade 1C)

Question 11

Platelet function monitoring

Answer 11

Recommendation 11 We suggest the use of POC platelet function devices as an adjunct to standard laboratory and/or POC coagulation monitoring in patients with suspected platelet dysfunction. (Grade 2C)

Question 12

Restricted volume replacement

Answer 12

Recommendation 13 We recommend use of a restricted volume replacement strategy to achieve target blood pressure until bleeding can be controlled. (Grade 1B).

Question 13

Vasopressors and inotropic agents

Answer 13

Recommendation 14 In the presence of life-threatening hypotension, we recommend administration of vasopressors in addition to fluids to maintain target arterial pressure. (Grade 1C) We recommend infusion of an inotropic agent in the presence of myocardial dysfunction. (Grade 1C)

Question 14

Tissue oxygenation

Answer 14

Recommendation 12 We recommend permissive hypotension with a target systolic blood pressure of 80–90mmHg (mean arterial pressure 50–60mmHg) until major bleeding has been stopped in the initial phase following trauma without brain injury. (Grade 1C) In patients with severe TBI (GCS ≤8), we recommend that a mean arterial pressure ≥80mmHg be maintained. (Grade 1C)

Question 15

Type of fluid

Answer 15

Recommendation 15 We recommend that fluid therapy using isotonic crystalloid solutions be initiated in the hypotensive bleeding trauma patient. (Grade 1A) We recommend the use of balanced electrolyte solutions and the avoidance of saline solutions. (Grade 1B) We recommend that hypotonic solutions such as Ringer’s lactate be avoided in patients with severe head trauma. (Grade 1B) We recommend that the use of colloids be restricted due to the adverse effects on haemostasis. (Grade 1C)

Question 16

Erythrocytes

Answer 16

Recommendation 16 We recommend a target Hb of 70 to 90g/L. (Grade 1C)

Question 17

Temperature management

Answer 17

Recommendation 17 In order to optimise coagulation, we recommend early application of measures to reduce heat loss and warm the hypothermic patient to achieve and maintain normothermia. (Grade 1C)

Question 18

IV. Rapid control of bleeding Damage-control surgery

Answer 18

Recommendation 18 We recommend that damagecontrol surgery be employed in the severely injured patient presenting with deep haemorrhagic shock, signs of ongoing bleeding and coagulopathy. (Grade 1B) Other factors that should trigger a damage-control approach are hypothermia, acidosis, inaccessible major anatomic injury, a need for time-consuming procedures or concomitant major injury outside the abdomen. (Grade 1C) We recommend primary definitive surgical management in the haemodynamically stable patient and in the absence of any of the factors above. (Grade 1C)

Question 19

Pelvic ring closure and stabilisation

Answer 19

Recommendation 19 We recommend that patients with pelvic ring disruption in haemorrhagic shock undergo immediate pelvic ring closure and stabilisation. (Grade 1B)

Question 20

Packing, embolisation and surgery

Answer 20

Recommendation 20 We recommend that patients with ongoing haemodynamic instability, despite adequate pelvic ring stabilisation, receive early surgical bleeding control and/or pre-peritoneal packing and/or angiographic embolisation. (Grade 1B) We suggest that the use of aortic balloon occlusion be considered only under extreme circumstances in patients with pelvic fracture in order to gain time until appropriate bleeding control measures can be implemented. (Grade 2C)

Question 21

Local haemostatic measures

Answer 21

Recommendation 21 We recommend the use of topical haemostatic agents in combination with other surgical measures or with packing for venous or moderate arterial bleeding associated with parenchymal injuries. (Grade 1B)

Question 22

Initial management of bleeding and coagulopathy Antifibrinolytic agents

Answer 22

Recommendation 22 We recommend that TXA be administered to the trauma patient who is bleeding or at risk of significant haemorrhage as soon as possible and within 3h after injury at a loading dose of 1g infused over 10min, followed by an i.v. infusion of 1g over 8h. (Grade 1A) We recommend that protocols for the management of bleeding patients consider administration of the first dose of TXA en route to the hospital. (Grade 1C) We recommend that the administration of TXA not await results from a viscoelastic assessment. (Grade 1B)

Question 23

Coagulation support

Answer 23

Recommendation 23 We recommend that monitoring and measures to support coagulation be initiated immediately upon hospital admission. (Grade 1B)

Question 24

Initial coagulation resuscitation

Answer 24

Recommendation 24 In the initial management of patients with expected massive haemorrhage, we recommend one of the two following strategies: FFP or pathogen-inactivated FFP in a FFP:RBC ratio of at least 1:2 as needed. (Grade 1C) Fibrinogen concentrate and RBC. (Grade 1C)

Question 25

VI. Further goal-directed coagulation management Goal-directed therapy

Answer 25

Recommendation 25 We recommend that resuscitation measures be continued using a goal-directed strategy, guided by standard laboratory coagulation values and/or VEM. (Grade 1B)

Question 26

Fresh frozen plasma-based management

Answer 26

Recommendation 26 If a FFP-based coagulation resuscitation strategy is used, we recommend that further use of FFP be guided by standard laboratory coagulation screening parameters (PT and/or APTT >1.5 times normal and/or viscoelastic evidence of a coagulation factor deficiency). (Grade 1C) We recommend that FFP transfusion be avoided in patients without major bleeding. (Grade 1B) We recommend that the use of FFP be avoided for the treatment of hypofibrinogenaemia. (Grade 1C)

Question 27

Coagulation factor concentrate-based management

Answer 27

Recommendation 27 If a CFC-based strategy is used, we recommend treatment with factor concentrates based on standard laboratory coagulation parameters and/or viscoelastic evidence of a functional coagulation factor deficiency. (Grade 1C) Provided that fibrinogen levels are normal, we suggest that PCC is administered to the bleeding patient based on evidence of delayed coagulation initiation using VEM. (Grade 2C) We suggest that monitoring of FXIII be included in coagulation support algorithms and that FXIII be supplemented in bleeding patients with a functional FXIII deficiency. (Grade 2C)

Question 28

Fibrinogen supplementation

Answer 28

Recommendation 28 We recommend treatment with fibrinogen concentrate or cryoprecipitate if major bleeding is accompanied by hypofibrinogenaemia (viscoelastic signs of a functional fibrinogen deficit or a plasma Clauss fibrinogen level ≤ 1.5 g/L). (Grade 1C) We suggest an initial fibrinogen supplementation of 3–4g. This is equivalent to 15–20 single-donor units of cryoprecipitate or 3–4 g fibrinogen concentrate. Repeat doses should be guided by VEM and laboratory assessment of fibrinogen levels. (Grade 2C)

Question 29

Platelets

Answer 29

Recommendation 29 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 ongoing bleeding and/or TBI. (Grade 2C) If administered, we suggest an initial dose of four to eight single platelet units or one aphaeresis pack. (Grade 2C)

Question 30

Calcium

Answer 30

Recommendation 30 We recommend that ionised calcium levels be monitored and maintained within the normal range during massive transfusion. (Grade 1C) We suggest the administration of calcium chloride to correct hypocalcaemia. (Grade 2C)

Question 31

Recombinant activated coagulation factor VII

Answer 31

Recommendation 31 We do not recommend the use of recombinant activated coagulation factor VII (rFVIIa) as first-line treatment. (Grade 1B) We suggest that the off-label use of rFVIIa be considered only if major bleeding and traumatic coagulopathy persist despite all other attempts to control bleeding and best-practice use of conventional haemostatic measures. (Grade 2C)

Question 32

VII. Reversal of antithrombotic agents Antithrombotic agent reversal

Answer 32

Recommendation 32 We recommend reversal of the effect of antithrombotic agents in patients with ongoing bleeding. (Grade 1C) 1. VKAs 2. Direct oral anticoagulants—FXa inhibitor 3. Direct oral anticoagulants—Thrombin inhibitor 4. Antiplatelet agents

Question 33

Reversal of vitamin K-dependent oral anticoagulants

Answer 33

Recommendation 33 In the bleeding trauma patient, we recommend the emergency reversal of vitamin K-dependent oral anticoagulants with the early use of both PCC and 5mg i.v. phytomenadione (vitamin K1). (Grade 1A)

Question 34

Direct oral anticoagulants—factor Xa inhibitors

Answer 34

Recommendation 34 We suggest the measurement of plasma levels of oral direct anti-factor Xa agents such as apixaban, edoxaban or rivaroxaban in patients treated or suspected of being treated with one of these agents. (Grade 2C) We suggest that measurement of anti-Xa activity be calibrated for the specific agent. If measurement is not possible or available, we suggest that advice from an expert haematologist be sought. (Grade 2C) If bleeding is life-threatening, we suggest administration of TXA 15mg/kg (or 1g) intravenously and that the use of PCC (25–50U/kg) be considered until specific antidotes are available. (Grade 2C)

Question 35

Direct oral anticoagulants—direct thrombin inhibitors

Answer 35

Recommendation 35 We suggest the measurement of dabigatran plasma levels using diluted thrombin time in patients treated or suspected of being treated with dabigatran. (Grade 2C) If measurement is not possible or available, we suggest measurement of the standard thrombin time to allow a qualitative estimation of the presence of dabigatran. (Grade 2C) If bleeding is life-threatening in those receiving dabigatran, we recommend treatment with idarucizumab(5 g intravenously) (Grade 1B) and suggest treatment with TXA 15mg/kg (or 1g) intravenously. (Grade 2C

Question 36

Antiplatelet agents

Answer 36

Recommendation 36 We suggest treatment with platelet concentrates if platelet dysfunction is documented in a patient with continued bleeding who has been treated with APA. (Grade 2C) We suggest administration of platelets in patients with ICH who have been treated with APA and will undergo surgery. (Grade 2B) We suggest that the administration of platelets in patients with ICH who have been treated with APA and will not undergo surgical intervention be avoided. (Grade 2B) We suggest that the administration of desmopressin (0.3 μg/kg) be considered in patients treated withplatelet-inhibiting drugs or von Willebrand disease. (Grade 2C)

Question 37

VIII. Thromboprophylaxis Thromboprophylaxis

Answer 37

Recommendation 37 We recommend early mechanical thromboprophylaxis with intermittent pneumatic compression (IPC) while the patient is immobile and has a bleeding risk. (Grade 1C) We recommend combined pharmacological and IPC thromboprophylaxis within 24 h after bleeding has been controlled and until the patient is mobile. (Grade 1B) We do not recommend the use of graduated compression stockings for thromboprophylaxis. (Grade 1C) We do not recommend the routine use of inferior vena cava filters as thromboprophylaxis. (Grade 1C)

Question 38

IX. Guideline implementation and quality control Guideline implementation

Answer 38

Recommendation 38 We recommend the local implementation of evidence-based guidelines for management of the bleeding trauma patient. (Grade 1B)

Question 39

Assessment of bleeding control and outcome

Answer 39

Recommendation 39 We recommend that local clinical quality and safety management systems include parameters to assess key measures of bleeding control and outcome. (Grade 1B)