The Next Big Thing. Dr Anne Weaver Consultant in Emergency Medicine & Pre-hospital Care Clinical Director for Trauma Royal London Hospital

Transcription

1 The Next Big Thing Dr Anne Weaver Consultant in Emergency Medicine & Pre-hospital Care Clinical Director for Trauma Royal London Hospital

2 Things to share with you Good conference / interesting journal Recent research PROPPR, FIinTIC, EFIT, Cryostat 1&2, ITACTIC Platelet storage TXA, DOACS The next big thing New gadgets / monitors

3 Vicky

4 THOR / RDCR network Transfusion journal annual supplement

5 International stats Trauma 4th leading cause of death globally 40% trauma deaths due to bleeding 2 million / yr worldwide Massive transfusion - 50% mortality Acute traumatic coagulopathy - 30% trauma pts ATC - 4 fold increase mortality

6 UK stats trauma haemorrhage 4700 / yr major haemorrhage (1550 dead) 1300 / yr massive haemorrhage (585 dead) Deaths 50% in 24hrs (50% in first 4 hrs) 50% needed urgent surgery 85 million / yr

7 Acute Traumatic Coagulopathy

8 Trauma Thrombin Fibrinolysis Fibrinogen Neuro-endocrine axis activated Protein C Fibrinolysis Shock Platelet dysfunction ACUTE TRAUMATIC COAGULOPATHY Hemodilution Resuscitation related Acidemia Hypothermia TRAUMA INDUCED COAGULOPATHY

9 Catastrophic haemorrhage in PHC C ABC Tourniquets Novel haemostatic agents Handling and packaging Splinting Permissive hypotension Damage control resuscitation / surgery thoracotomy / REBOA Blood product transfusion TXA administration

10 CODE RED pre-alert system Often for non-compressible haemorrhage Make a clinical judgment of injury load Determine the presence of shock physiology Activation of Massive Haemorrhage Protocol

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12 2.8 units prbc transfused On-scene time 37 mins Hb 14.0 ph 7.07 BE 12.8

13 Pre-hospital PRBC trials PRBC Improved outcomes 6hr survival 24hr survival Reduced blood product transfusion in 24hrs Improved BE / acid base balance on admission Feasible Scandinavia / Australia / US / UK Low wastage

14 Does 1:1 improve outcome? Borgman et al. J Trauma 2007; 63: Kashuk et al. J Trauma 2009; 65:

15 Plasma Contains plasma proteins, clotting factors, fibrinogen Volume resuscitation Haemostatic resuscitation Restores glycocalyx Available as: Fresh Frozen Plasma (FFP) thawed for use (delay) Lyophilised / freeze dried plasma reconstituted, not licensed in UK Liquid plasma never frozen, contains platelets, 7 day shelf life

16 Pre-hospital plasma in practice Trials in US - PAMPER, COMBAT, PUPTH Feasible but high wastage due to short shelf-life extended to 5 days in April 2016 Wales & Thames Valley AA thawed plasma France, Germany, Kent / Surrey & Sussex freeze dried plasma If born after 1st Jan 1996 to avoid CJD, cannot have UK plasma give DOB if known in pre-alert.

17 VS.

18 PROPPR (plasma, platelet, RBC) trial Multi-centre RCT 1:1:1 vs 1:1:2 Low numbers No stat sig difference in 24 hr or 30 day mortality Higher rate of haemostasis Reduced numbers of death due to exsanguination UK National guidelines changed on this basis last year (2015) MHPs should be aligned to this ratio

19 Platelets We were told: Stored at room temperature, constant agitation We weren t told: that they have better function at 4C Shortened time in circulation but that s ok for severe bleeding Cold platelets might be useful in trauma

20 Fibrinogen

21 Impact of fibrinogen levels on outcomes after acute injury in patients requiring a massive transfusion. Inaba K et al. J Am Coll Surg Feb;216(2): Fibrinogen > 180 mg/dl, Fibrinogen mg/dl, Fibrinogen < 100 mg/dl

22 Hyperfibrinolysis

23 Fibrinogen concentrate or cryoprecipitate Fibrinogen Takes a while to mix esp high dose Expensive Only contains fibrinogen Easy to carry / store at room temp Not currently licensed in UK Cryoprecipitate Has to be thawed but is ready mixed Contains other factors vwf, XIII, fibronectin Relatively cheap Research re shelf-life of prethawed cryo - up to 14/7

24 Fibrinogen RCT

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27 CRYOSTAT a

28 CRYOSTAT Mortality a Standard: Y 6/21 : 28% Early CRYO: 2/20 : 10%

29 CRYOSTAT 2

30 Tranexamic Acid

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32 Tranexamic acid - standard practice 1 g bolus followed by 1 g infusion over 8 hrs Benefit if given within 3 hrs Optimal results if within 1 hr Maximal effect for SBP <75mmHg Potentially harmful if delayed >3hrs Trial data showed no increase in arterial or venous thrombosis

33 Royal London research team data First dose of TXA is effective for most patients Visible reduction in hyperfibrinolysis on ROTEM 2 nd dose (infusion) may not be required in many cases If hyperfibrinolysis persists need to provide more substrate ie Fg Code Red pts who receive TXA have 10% VTE rate (much higher than control group) Suggestion from US group that TXA should be more targeted than current practice and guided by ROTEM / TEG. Moore E et al Transfusion 2016;56(Suppl 2):S

34 itactic Implementing Treatment Algorithms for the Correction of Trauma Induced Coagulopathy Prospective, randomised controlled trial Bleeding trauma patients ROTEM / TEG vs conventional clotting tests (CCT)

35 Visco-elastic assays ROTEM TM TEG

36 5 minute diagnosis ATC

37 itactic Implementing Treatment Algorithms for the Correction of Trauma Induced Coagulopathy FIBRINOGEN If FIBTEM CA5 < 10mm Give additional 4g equivalent of fibrinogen (As Cryoprecipitate or Concentrate) PLATELETS If (EXTEM CA5 - FIBTEM CA5) < 30mm Give 1 additional pool of platelets PLASMA If EXTEM CA5 >40mm AND EXTEM CT >80s Give 4 additional units of plasma TRANEXAMIC ACID If EXTEM LI30 <85% Give additional 1g IV bolus of tranexamic acid

38 NOACS / DOACS (Non-vitamin K dependent / Direct oral anti-coagulants) Eg Dabigatran, Rivaroxaban

39 Novel anti-coagulants

40 Dabigatran antidote Idarucizumab (Pradaxa, Praxbind) Available in a pharmacy near you?? Better if it was in a cupboard in resus or in your Thomas pack Interim results of a phase III trial Pollock et al Immediate reversal of dabigatran by binding to drug & metabolites IV drug 5g ( 2 x 50 ml bolus over 20 minutes) 2400 Dose can be repeated May need blood product support to control bleeding

41 Blood product transfusion in PHC Ratios debate ABO compatability and availability Temperature storage of components Safety leuco-reduction Cold storage loss of platelet function?? Feasibility packaging, licensing, cold chain, traceability

42 Treating blood failure we need a fluid that can Repay oxygen debt PRBC, crystalloid Stop proteolysis - plasma Repair glycocalyx plasma, platelets Treat coagulopathy plasma, cryo, TXA, platelets And restores volume as quickly as possible

43 The Next Big Thing 1:1:1 Plasma: PRBC: platelets Through one IV line No mixing with water Leuko-depleted with platelet sparing filter No UK production chain currently

44 Transfusion. 2016:56;S190-S202 US Army data WB superior or equivalent to blood product txn 4C platelets have better function than 22C plt

45 Norway (PHC and special forces) Military-civilian co-operation Freeze dried plasma 2013 PRBC 2014 Whole blood 2015 (Special forces only) Warm, whole blood donation to buddy Pre-screened personnel Fit to continue special ops work after donation Developed protocol for Emergency Donor Panels Rapid blood group 40s Blood borne virus screen 60s

46 New gadgets / monitoring Compensatory Reserve Index monitoring (Convertino physiologist) In development Could be used to select Special Forces recruits with better reserve Red / amber / green indicator Accurate predictor of reserve Could be added to traditional monitors J App physiol 2013;115: ROTEM sigma model Easier to use than previous Delta version Perhaps much smaller version in future for PHC use

47 Ongoing work for bleeding patients Research trials rapidly translate to clinical practice Whole blood bench work prior to RCT in civilian pre-hospital care setting Improve processes & procedures Ambulance service dispatch and advice to bystanders Right turn resuscitation direct to theatre Hospital design RAPTOR suites Mass Casualty events Stock planning / product type Emergency Donor panels

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49 ROYAL LONDON HOSPITAL MTC CODE RED MORTALITY

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