CRASH ing Trauma Patients: The CRASH trials. Tim Coats Professor of Emergency Medicine University of Leicester, UK

Transcription

1 CRASH ing Trauma Patients: The CRASH trials Tim Coats Professor of Emergency Medicine University of Leicester, UK

2 I DO NOT have an affiliation (financial or otherwise) with a pharmaceutical, medical device or communications organization.

3 I give TXA to every patient who might be bleeding. I give TXA to every trauma patient if I send off a G+S I give TXA to every trauma patient who I cross match I use TXA as part of my massive transfusion protocol for trauma

4

5 ACOT a new concept in trauma care Abnormal clotting related to death Mortality (%) >59 Injury Severity Score Normal Coagulopathy Brohi, Singh, Heron and Coats

6 Early tissue factor release

7 Early clot formation

8 BUT - also early clot breakdown

9 A large randomised controlled trial among trauma patients with significant haemorrhage, of the effects of anti-fibrinolytic treatment on death and transfusion requirement

10 CRASH2 trial - 30 day mortality TXA-allocated (n= 10,060) 1,463 (14.5%) Placebo-allocated (n= 10,067) 1,613 (16.0%) Risk ratio (95% CI) 0.91 ( ) P= TXA better TXA worse

11 Moderate injuries benefit

12 Question Which patient group contains more trauma patients who die from bleeding?: - 1) Moderately injured (probability of death 6 20%) - 2) Very severely injured (probability of death > 50%)

13 Give TXA in moderate injury Risk strata Total patients n Deaths n (%) Number needed to treat Proportion of total deaths <6% 6, (1.2) % 4, (12) % 1, (38) >50% (70) All patients 13, (13)

14 Time effect TXA in trauma Early treatment is better:

15 The latest management guide Acute Traumatic Coagulopathy what s the latest? Difficult to separate: - 1) The management of coaguloapthy - 2) The control of bleeding. - 3) Optimisation of tissue oxygenation Critical Care 2013;17:R76 - Management of bleeding and coagulopathy following major trauma: An updated European guideline -

16 Coagulation system Sequence of cascades Intrinsic system, Extrinsic system, Common pathway Endothelium, Platelets, Blood Exquisitely regulated dynamic balances Yin and yang of clot making and clot breaking Clot making activates clot breaking

17 Question What proportion of clot formation does your coagulation screen monitor? A) 4% B) 20% C) 50% D) 100% The first 4%

18 How can you learn more about the state of your patient s coagulation system?

19 Is TEG telling us stuff? 70 Change from Control ACT (s) Saline Gelofusin % 10% 20% 30% 40% 50% 60%

20 Is TEG telling us stuff? Change from Control Time to Peak (s) Gelofusin Saline % 10% 20% 30% 40% 50% 60%

21 Our Education Initiation, Propagation, Maturation, Lysis. Coagulation screen measures Initiation only Coagulation as a dynamic balance

22

23

24

25 In the crystal ball Resuscitating the endothelium A very large organ Source of all badness in the world An endothelium preserving resuscitation strategy?

26 Summary Use TXA in trauma patients who might be bleeding - All those who have a G+S taken. Coagulation is important we need to think about it in a different way Enter your patient into a clinical trial

27 ?

28 Encore - Question If TXA prevents bleeding why doesn t it reduce the amount of blood used?

29 Survival Bias and Ratios If you live you use more blood So if a trial has a big mortality effect you cannot assess the effect on blood usage (Interaction between the primary and secondary outcomes) CRASH2 TXA has no effect on blood product usage

30 Question How about the evidence from databases that a 1:1 ratio FFP:Blood is better?

31 If blood given before FFP patients who die early will have more blood and less FFP If FFP given before blood patients who die early will have less blood and more FFP Retrospective reviews cannot determine the best ratio

32 Question What type of research does emergency medicine need?

33 Pragmatic or Explanatory? Clinicians are brought up on explanatory research Why? is considered a crucial question Emergency Medicine is a very practical speciality What works? is more important than Why?

34 explanatory approach Tight entry criteria (lots of exclusions) - Homogeneous patient group Non-trial treatments tightly controlled Smaller sample size (small complex trial) Performed in academic centre Result: - Difficulty in generalisation to other patients - Results not so good in other centres - More work needs to be done in other groups - Different physicians use the treatment in different ways - Meaningful economic analysis not possible

35 pragmatic approach Entry based on broader criteria No control of non-trial management Large sample size (Large simple trial) Often performed across many centres Accept variation - embrace variation! Results - Easy to generalise - Real world estimate of benefit - Subgroups may be not benefit / harmed - Economic analysis can be performed

36 Example CRASH2 entry criteria First the search for the definition BP / mechanism / blood transfused / etc Just didn t work Then the pragmatic realisation: Enter the patients who you would treat. Those who you think are bleeding or at risk of bleeding.

37 Generalisability CRASH3 was a Pragmatic trial The result is generalisable we know what to do. It doesn t tell you why!

38 Summary Use TXA in trauma patients who might be bleeding - All those who have a G+S taken. Coagulation is important we need to think about it in a different way Enter your patient into a clinical trial