Prise en charge de la transfusion massive en chirurgie programmée et chez le polytraumatisé

Transcription

1 Cours de sciences de base en anesthésiologie 2010 Prise en charge de la transfusion massive en chirurgie programmée et chez le polytraumatisé Jean-François Hardy MD, FRCPC Département d anesthésiologie Centre Hospitalier de l Université de Montréal

2 + importante mise à jour pour l évolution des connaissances depuis 2006

3 Objectives To review the pathophysiology of disturbed hemostasis in massively transfused patients in elective surgery and trauma Accordingly, to describe the management of massive transfusion in o Elective surgery o Trauma

4 Massive transfusion in elective surgery Tissue trauma is controlled Initiation of transfusion is rapid Normovolemia is maintained Normothermia is maintained Monitoring of hemostasis is ongoing Coagulopathy is a late event

5 Crystalloids and colloids Hemodilution Hb, coagulation factors and platelets But rapid hemodilution with crystalloids coagulation (TEG) o Clinical significance remains unclear Colloids may affect hemostasis o Colloids not recommended by the American College of Surgeons

6 Characteristics of colloids and their effects on hemostasis (adapted from B. Ickx et al.) Product Commercial name Concentration % Oncotic pressure mmhg Initial volume expansion % Persistance in the body (days) Maximal dose/24h Effect on hemostasis Albumin Dextran 70 Macrod ex g/kg +++ Dextran 40 Rheomacrod ex g/kg +++ Modifi ed fluid gelatin Gelofusine, Plasmion to + Urea linked gelatin Hemacel to + Hespan HES 450/0.7 Plasmasteril ml/kg +++ HES 200/0.62/10 Elohes ml/kg ++ HES 200/0.5/5 Hesteril ml/kg + Pentaspan 28 ml/kg HES 200/0.5/5 Lomol, Hesteril ml/kg + HES 130/0.4/11 Voluven ml/kg 0 to +

7 Erythrocytes and hemostasis: Rheological mechanisms Hematocrit > 30% Flow of blood RBC Platelet Eberst and Berkowitz, Am J Med 1994

8 Anemia and hemostasis: margination of platelets Hematocrit < 25% Flow of blood RBC Platelet Eberst and Berkowitz, Am J Med 1994

9 Optimal hematocrit for hemostasis? Hematocrit correlates with the BT o In rabbits, BT when the Hct < 35% o In humans, the BT 60% when HCT 15% UF to Hct (36-42%) transfusions in pediatric CPB The optimal Hct to sustain hemostasis in the bleeding patient is unknown

10 Coagulation factors Prior to 1990 (approximately) o Fresh, stored or modified whole blood o Labile coagulation factors not a problem o o

11 Coagulation disorders in combat casualties During sequential transfusions fibrinogen levels in peripheral blood fell slightly. There was no fall below normal in any patient. The mean platelet count remained about 100 G/L after the first 6L of blood. Admission Units transfused No clinical evidence of hemorrhagic diatheses appeared in any of these young men despite large volumes of transfused blood Simmons RL. Ann Surg 1969;169:455-82

12 Coagulation factors o o Since 1990 o Use of packed red cells (30-60 ml of plasma) o Coagulation factors have become an issue

13 Things change after Laboratory hemostatic abnormalities in massively transfused patients given red blood cells and crystalloid These data suggest that coagulation factor replacement is necessary in patients who receive 12 or more units of PRBC or cell-saver blood, and platelet replacement is necessary in patients who receive 20 or more units of any red blood cell product 1.5 x mid-range of normal Leslie & Toy. Am J Clin Pathol 1991;96:770-3

14 Coagulation changes during packed red cell replacement of major blood loss Platelet transfusions were ineffective in patients with a low fibrinogen concentration. MVB stopped after 4 and 2 units of FFP. Murray DJ. Anesthesiology 1988;69:839-45

15 Platelets and hemostasis In anesthesia, the focus has been on platelets: o Plt counts are decreased in pts who bleed BUT o Plt counts are similar whether pts bleed or not Importance of: o Coagulation factors (specially fibrinogen) o Red cells o Temperature

16 Coagulation defects associated with massive blood transfusion the observed mean platelet counts parallel the predicted platelet counts based on a standard washout equation No! not parallel, indicating the influx of sequestered or young platelets in the circulation Miller RD. Ann Surg 1971;174:

17 Prophylactic platelet administration during massive transfusion There was no difference in platelet counts in patients receiving platelet concentrates or FFP Prophylactic therapy with platelet concentrates was ineffective in preventing diffuse microvascular bleeding Reed RL. Ann Surg 1986;203:40-8

18 Coagulopathy of MT in elective surgery In summary Dilution o Red cells o Coagulation factors o Platelets Coagulopathy o Infrequent o Late event

19 Massive transfusion in trauma Tissue trauma is massive and uncontrolled Initiation of transfusion may be late Hypovolemia and shock are present Temperature is not controlled => hypothermia Monitoring of hemostasis is late Coagulopathy occurs early on

20 Coagulopathy => Microvascular bleeding Often complicates the management of MT Relates to: o The nature and importance of tissue trauma: brain trauma - ISS > 25 o Shock and tissue anoxia: ph < SBP < 70 mmhg o Hypothermia: temperature < 34 C Incidence of coagulopathy = 98% if all factors + Cosgriff N. J Trauma 1997;42:857-62

21 Hypothermia, acidosis, coagulopathy & MT 45 trauma pts 15 deaths 30 survivors ISS Lowest Temp C * C Lowest ph * Lowest plt count 58 7 G/L 59 6 G/L Highest aptt sec 47 5 sec Clinical coagulopathy 73%* 23% PRBC U * U * P<O.05; Hypothermia + acidosis bleeding despite adequate blood, plasma & platelet replacement Ferrara, A. Am J Surg 1990; 160:515-8

22 Temperature: hypothermia Hypothermia o Slows the coagulation cascade o Reduces the synthesis of coag. factors o Increases fibrinolysis o Causes a reversible platelet dysfunction o Prolongs the BT Important contributor to coagulopathy in trauma patients

23 Hypothermia and coagulation in rats What we see What we should see Reed RL. J Trauma 1992;33:465-70

24 Anticoagulation

25 Hyperfibrinolysis PAI- 1 Consume d by apc tpa released by endothelium

26 In summary

27 Systemic compromise The road to coagulopathy Microvascular Bleeding Trauma patient Elective surgery Transfusion

28 Monitoring of coagulopathy No simple & reliable test available Bleeding time o Increases early during surgery & transfusion o Remains elevated several days o Does not discriminate between bleeding and non-bleeding patients o BT = useless

29 Platelet count Readily available via automated counters Low platelet count platelet transfusion Must be interpreted in context: o Hypothermia? o Expected platelet function? o Hemoglobin concentration? o Fibrinogen concentration?

30 PT and aptt Require centrifugation = delays Increases are very common Factor levels related to hemodilution Marked prolongations (1.5 to 1.8 x control) o Predict factor V and VIII < 30% o Correlate with MVB Again, must be interpreted in context Ciavarella D. Br J Haematol 1987;67:365-8

31 Monitoring devices Numerous devices are available but none has been demonstrated to be of any use during massive transfusion

32 Basic management of the bleeding patient Correct hypothermia Transfuse red cells (optimal Hct?) Transfuse FFP o For a markedly prolonged PT/aPTT o To correct a low fibrinogen concentration (consider cryoprecipitate if ineffective) Transfuse platelets o Decreased number o Decreased function

33 Massive transfusion in the elective surgical setting Erber WN. Transfus Apheresis Sci 2002;27:83-92

34 Massive transfusion in trauma The recent military experience suggests «damage control resuscitation» «Damage control surgery» Minimal use of crystalloids RBC:FFP:Plts in a 1:1:1 ratio Specific demographic characteristics Healthy and young (21-30y) males Combination of blast and penetrating injury

35 Mais qu en est-il de la transfusion massive chez les civils? - traumatisés - non traumatisés

36 Revue de 2002 à pts transfusés massivement 250 pts transfusés 1 10 culots

37 Diminution de la mortalité chez les patients transfusés massivement (P =.001)

38 Pas de bénéfice clair chez les patients moins transfusés (P =.06)

39 Retrospective analysis of 713 trauma patients admitted between 2002 and 2006 with serious injury (ISS > 16) massive transfusion (RBC > 10) Note: - relatively old population (mean age 40y) - largest proportion of females (30.3%)

40 RBC : FFP RBC 18 : FFP 18 RBC : FFP < 0.9 RBC 17 : FFP 26 RBC : FFP > 1.1 RBC 20 : FFP 11

41 Mortality decreased with a RBC to FFP ratio < 0.9 but ventilator days and LOS increased (TRALI?)

42 Review of 466 MT pts from 16 trauma centers July 2005 June 2006 Authors recommend a 1:1:1 ratio of plasma:platelets:rbc

43 Survival at 24h and 30 days P =.08

44 o Trauma pts admitted directly to ICU within 24h of surgery o In 250 pts transfused 1 U RBC, FFP:RBC ratio did not predict any outcome factor o In 81 pts transfused 10 U RBC, FFP:RBC ratio did not predict any outcome factor

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46 Limites des études Études rétrospectives o «Survivorship bias»: les pts qui sont morts <2h n ont pas eu le temps de recevoir du FFP o «Ascertainment bias»: difficulté à colliger des données valides dans un environnement extrême Différences entre civils et militaires o Importantes différences démographiques o Traumas pénétrants vs. traumas non pénétrants o Diponibilité des produits sanguins

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48 Treat the «acute coagulopathy of trauma» which is present in many patients even before the start of resuscitation Environ 25% des traumas ont une coagulopathie à l arrivée: PT > 18s; PTT > 30s Mortalité 46% vs. 10,9% Marqueur ou déterminant? Pas de démonstration que le traitement améliore le pronostic

49 Inappropriately triggering the use of formula-driven care on non-massive transfusion patients where RBC alone would have been sufficient Environ 17% des traumas civils sont transfusés 2-5% des patients sont transfusés massivement > 10 U Le protocole 1:1:1 ne s applique donc qu à un très petit nombre de patients Trauma 1:1:1

50 Utilization of formula-driven care in nontrauma settings with unknown risks and benefits Le protocole 1:1:1 ne s applique pas en chirurgie programmée Conduite suggérée demeure o Crystalloides + GR o Monitorer la coagulopathie o PFC pour PT/PTT < 1,5 x normale (dose usuelle 3-6 unités) o Plaquettes pour > 50 G/L Transfusion de GR 1:1:1

51 «At a state of clinical equipoise» Pas de démonstration claire (non-équivoque) des bénéfices ou des inconvénients d un ratio fixe 1:1:1 Besoin d études prospectives randomisées Mieux comprendre la coagulopathie du trauma/de la transfusion massive Outils diagnostiques performants requis

52 Case record review of 65 pts undergoing emergency AAA surgery On admission: PC < 150 G: 93% mortality PC 150 to 250 G: 30% mortality PC > 250 G: 17% mortality After surgery Improved outcome (death and MOF) if PC > 100 G PC is a simple marker of outcome in AAA patients J Vasc Surg 1995;21:484-91

53 Prospective observational study of 20 AAA patients Perioperative fall in vwf and PC PC significantly lower in non-survivors Low vwf and PC may represent consumption secondary to macro and microvascular thrombus formation Eur J Vasc Endovasc Surg 2003;26:412-7

54 50 pts received aggressive transfusion protocol vs 93 controls 5 PRBC + 5 FFP (always 1:1 ratio) + 2 pooled PC on diagnosis 2 pooled PC prior to unclamping and if bleeding persisted Intervention group: higher PLT count: 155 vs 69 G + shorter apttt fewer postoperative transfusions (p < 0.01) higher 30 day survival rate (66 vs 44%; p = 0.02) Proactive PC and FFP improve coagulation, decrease hemorrhage and increase survival in ruptured AAA Transfusion 2007;47:593-8

55 Recombinant factor VIIa Successful in case reports/case series Rescue (off-label) therapy for massive bleeding Localized generation of thrombin Requires clotting factors and platelets Incidence of thromboembolic events? One RCT in trauma Very expensive

56 Boffard KD et al. J Trauma 2005;59:8-18 rfviia: main results No decrease in transfusion (primary outcome) by Intent-to-Treat analysis In patients who survived 48h: o Mean reduction of 2.6 U in the «Blunt» group (P = 0.02) o Mean reduction of 1.0 U in the «Penetrating» group (P = 0.10) No decrease of ARDS, MOF and/or death No increase of TE adverse events In summary: modest benefits in this study

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59 Conclusions Coagulopathy of MT o Intricate, multicellular and multifactorial o Infrequent and late event in elective surgery o More frequent in trauma (shock, acidosis, hypothermia) Mechanism is unclear Management o Red cells to raise the Hct o FFP to correct a low fibrinogen/factor level o Platelets to correct low/ineffective platelets o Order/quantity may vary according to context Monitoring o Reliable POC monitors of coagulation needed