AVANCOS no TRATAMENTO da HEMORRAGIA MACICA

Transcription

1 AVANCOS no TRATAMENTO da HEMORRAGIA MACICA Sandro Rizoli, MD PhD FRCSC FACS Professor Associado Cirurgia & Medicina Intensiva De Souza Trauma Research Chair Chefe Regiao XII Comite de Trauma Colegio Americano Cirurgioes

2 Toronto Canada Imigrantes 4 milhoes 6,500 Brasileiros

3 Bleeding Common Cause of Death 6,000 trauma deaths/year Canada 4% CNS + Exsanguination 1% Other 4% Organ Failure 40% CNS 51% Exsanguination & Coagulopathy Sauaia et al J Trauma 1995;38:185

4 Trauma Bleeding is Common Sunnybrook 1100 traumas/year 30% transfused RBC 4% massive transfusion (50-60 patients) >50% 3,000U FFP 90% 772U cryo

5 Massive Bleeding Familiar to most surgeons Trauma surgeon 1 ary responsibility Novel management trauma UGI bleed NEJM 2008; 358:178 Post-operative bleeding Critical Care bleedings Mediastinal hematoma

6 Publication Explosion Trauma and Blood Transfusion

7 Avancos Tratamento Hemorragia Macica 1. Ressuscitacao com formula 1:1:1 2. Fibrinogenio ao inves de plasma 3. Protocolos para transfusao macica 4. Anti fibrinoliticos

8 Formula driven resuscitation or 1:1:1 damage control resuscitation

9 Current Resuscitation - Massive Bleeding Crystalloid-based resuscitation Directed by lab Hg >70g/L FFP INR<1.5 Plat >50x10 9 /L Cryo fibrinogen>1g/l Limitations Lack evidence Treat coagulopathy late Patients coagulopathic Poor results (1 st cause death)

10 Damage control resuscitation FFP 1:1 RBC Massive bleeding Start with blood RBC 1:1 FFP:1 platelet Thawed plasma 24/7 Treat coagulopathy from start

11 Evidence on FFP 1:1 RBC Borgman (J.Trauma 2007;63:805) Retrospective 246 US Military 10U RBC/24h (including whole blood) FFP:RBC mortality death by exsanguination 1:8 65% 92% 1:2 34% 78% 1:1 19% 37%

12 Evidence on FFP 1:1 RBC Problems 1. Too good to be true: drop mortality 50% Borgman (J.Trauma 2007;63:805) Data quality (retrospective) Survivorship bias FFP:RBC mortality time to death 1:8 65% 2h 1:1 19% 38h

13 Evidence on FFP 1:1 RBC Problems 1. Too good to be true: bias Snyder (J.Trauma 2009;66:358) Retrospective; 134 patients; 10U/24h Ratio at 24h vs. time-dependent variable Does 1:1 really improve survival?

14 Damage Control Resuscitation Initial report = drop mortality 1:1:1 Conventional Duschene 26% 88% Maegele 24% 46% Holcomb 40% 60% Kashuk 8% 40% Scalea No difference Teixeira 26% 90% Zink 26% 55% Median 26% 55% =29% USA trauma centers adopted DCR

15 Evidence on FFP 1:1 RBC Problems 2. FFP to wrong patients: collateral damage 1,685 trauma patients given <10 RBC 30.6% FFP in 12h 284 matched pairs 2.9U RBC 3.0U FFP Number needed to harm 12 Inaba K, J Am Coll Surg 2010; 210:

16 Sunnybrook Trial 1:1:1 vs. laboratory-guided Trauma Formula-Driven vs. Lab-Guided Transfusion Study - TRFL Jeannie Callum Barto Nascimento

17 TRFL Preliminary Results 35 patients - 16 months 32 patients 3 excluded 1:1:1 = 18 patients Lab = 14 patients 1:1:1 in 75% ratio 1.2:1:1 MT = 40% 17% death Lab q2h in 100% ratio 2:1:0.6 MT = 83% 14% death (24h)

18 Avancos Tratamento Hemorragia Macica CONCLUSOES: Ressuscitacao com formula 1:1:1 Nao descongele plasma por enquanto!

19 Fibrinogen Concentrates The next trend? 16 grams 9 grams 12 grams Acta Anaesthesiol Scand. 2010;54: Epub 2009 Oct 26 Anaesthesia. 2010;65: Epub 2009 Nov 30 Scand J Clin Lab Invest. 2010;70:453-7

20 Fibrinogen as per FIBTEM Schochl H et al. Critical Care 2010; 14: R55 Retrospective analysis of trauma patients transfused >5 u/24 hours They use ROTEM to decide what to give Increase FIBTEM MCF 2-4 g fibrinogen Increased EXTEM MCF Platelets Increased EXTEM CT PCC IU When do they give FFP?

21 Fibrinogen as per FIBTEM Schochl H et al. Critical Care 2010; 14: R55 N=149 patients over 4 years RBC>5/24 Excluded 15 that died in <60 min and 3 that got nothing but RBC Severely injured mean ISS 38 Median 10 RBC/24 hours Only 3/131 did NOT get fibrinogen concentrates! (median 7 g/24 hours) 0.8g:RBC 30 treated with PCC, 21 FFP, 29 platelets! Predicted mortality 34%, observed 24%

22 Avancos Tratamento Hemorragia Macica CONCLUSOES Ressuscitacao com formula 1:1:1 Fibrinogenio ao inves de plasma Mesmo grau evidencia que 1:1:1

23 The pre- and post-mtp studies Riskin DJ et al Am Coll Surg Aug;209(2): Most Centers North America have MTP Goal: provide 1:1:1 Group: Blood Banks + surgeons + OR + ER Review 2y before/after MTP implementation 4,223 vs. 4,414 patients (>10U RBC) 1:1.8 vs. 1:1.8 BUT 45% vs. 19% mortality Conclusion: MTP reduces mortality (????)

24 Military Before, After Simmons JW, et al. J Trauma 2010; 69: S They were able to change transfusion practice

25 Miltary Before, After (n=777) Simmons JW, et al. J Trauma 2010; 69: S Militaries successfully managed patients better BUT P=0.12

26 Avancos Tratamento Hemorragia Macica CONCLUSOES Resuscitacao com formula 1:1:1 Fibrinogenio ao inves de plasma Protocolos para ressuscitacao Protocolo nao; prepar reduz mortalidade!

27 Anti fibrinolytic reduces mortality CRASH 2 Lancet 2010; 376(9734): patients in 40 countries Risk of significant bleeding 1g in 10min + 1g in 8h 4w mortality = 14.5% vs. 16% Mortality bleeding = 4.9% vs. 5.7% Tranexamic acid reduces risk of death

28 Avancos Tratamento Hemorragia Macica CONCLUSOES Ressuscitacao com formula 1:1:1 Fibrinogenio ao inves de plasma Protocolos para transfusao macica Anti fibrinoliticos T.A. bom, bonito e barato = vale a pena

29 Summary Lots of great ideas, lots of hype, but no clear winners 1:1:1 ou DCR: individualize + goal directed Requer plasma descongelado Transfunde quem nao precisa Fibrinogenio: cedo para mudar Protocolos: otima ideia Protocolo nao reduz mortalidade Preparacao e o mais importante Tranexamic: barato, seguro, reduz morte

30 RESIDENT Resident GUIDANCE guidance RECOMMENDED suggested FOR WACKY STATISTICAL METHODS 1 st RCT rviia Conclusion: Recombinant FVIIa resulted in a significant reduction in RBC transfusion in severe blunt trauma. Similar trends were observed in penetrating trauma. The safety of rfviia was established in these trauma populations within the investigated dose range. KD Boffard, B.Riou, B.Warren et al. J.Trauma. 2005; 59:8-18 Boffard KD, et al. J Trauma. 2005;59:8-15

31 No Effect on Transfusion Rate Boffard KD, et al. J Trauma. 2005;59:8-15 RBC RBC Control R7a Blunt 7.2 u 7.8 u Penetrating 4.8 u 4.0 u * p=0.07

32 Exclude patients who bled to death in the 1 st 2 days?

33 Recombiant Factor VIIa - CONTROL Hauser CJ, et al. J Trauma 2010; 69: Prospective, randomized, double-blinded, multicenter trial (150 hospitals in 26 countries) 3 doses r7a 200/100/100 ug/kg - $30K Up to age 70 Still bleeding with shock/hypotension/acidosis after 4 units RBC

34 Recombinant Factor VIIa - CONTROL Hauser CJ, et al. J Trauma 2010; 69: Powered to detect 16.7% mortality reduction assuming a 30% baseline mortality Planned interim analysis Stopped early due to high likelihood of futility 573 enrolled, 560 dosed, 554 in ITT No difference in mortality (11% vs. 11%)

35 Safety Profile n= 4119 Levi M, et al. NEJM 2010; 363: Arterial TE events were more common in r7a treated patients OR 1.68 ( , p=0.003) Risk attributed to patients over 65 years yrs OR 2.12 ( , p=0.07) >75 yrs OR 3.02 ( , p=0.02)