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international collaboration:
Tel HashomerMedical University of TelAviv, Israel US Army, Fort Sam Houston, Texas, USA Coalition Warefare Program - US Army Dept. of Bioengineering, Univ. of San Diego, USA
conflict of interest:
Astra Zeneca, Baxter, Braun, Biotest, CSL Behring, Delta Select, Dade Behring, Fresenius, Glaxo, Haemoscope, Hemogem, Lilly, LFB, Mitsubishi Pharma, NovoNordisk, Pentapharm
Vicious Circle
coagulopathy
blood loss
hypovolemia
Morbidity/Mortality
transfusion
dilution
Fluid therapy in haemorrhagic shock? Massive Transfusion Protocols Target Controlled Bleeding Management
Immediate versus dalayed fluid resuscitation for hypotensive patients with penetrating torso injuries
Bickell W.H. et al. NEJM 1994; 331: 1105-9
n = 598 patients age: 31a 11 systolic blood pressure: 90 mmHg penetrating chest trauma immediate fluid resuscitation (n= 309): 62% survivors delayed fluid resuscitation (n=289): 70% survivors p=0.04 !!!
Non Survivor
193
1 patient
116 86
203
p=0.04
Non Survivor
193 202
116 87
p=0.057
Immediate versus dalayed fluid resuscitation for hypotensive patients with penetrating torso injuries
Bickell W.H. et al. NEJM 1994; 331: 1105-9
immediate fluid resuscitation (n= 309): 62% survivors delayed fluid resuscitation (n=289): 70% survivors p=0.04
but : ... 22 patients within the delayed group received fluid 70 patients died before surgery (41/29)
SBP > 100 mmHg active bleeding (n.s.) death predicted survival actual survival 4 94% 92,7%
infusion - why?
MAP = CO x SVR DO2: CO x CaO2 CaO2: (Hb x SaO2 x 1,34) + (pO2 x 0,003) improvement of perfusion and peripheral oxygenation
Hypovolemia
blood volume CO and DO2 macrocirculation
septic shock
800 1.000 mL
Endotoxemia
300 2.000 mL
100 1.000 mL
ischemia
MOF
gut, kidney,
increased pT and apTT due to increased BE Increased BE: high thrombomodulin and decreased protein C
12 h 24 h
24 h
0,5 1,0 5
K 4-5 2
Ca 5 3
British Consensus guideline on Intravenous Fluid Therapy for Adult surgical Patients
acidosis is associated: cardiac failure, higher morbidity and mortality. Persistent OH is associated higher rates of RC, MSOF, and death. Blow O: J Trauma (1999) 47:964
Fluid therapy in haemorrhagic shock? Yes! Massive Transfusion Protocols Target Controlled Bleeding Management
Pro A retrospective analysis from the Trauma Registry of the Deutsche Gesellschaft fr Unfallchirurgie M. Maegele et al. Vox Sanguis 2008
retrospective analysis German Trauma Registry ISS > 16 >10 RBC (ER ICU) n = 484 mean age 40,1 years mean ISS 41
RBC:FFP = 1:1 Sepsis, MOF RBC:FFP < 1:1 ventilator days, ICU- and hospital stay
Ambiguous Crude Complication Rate Comparison for Patients Who Received a High FFP vs. a Low FFP: Transfusion Ratio
70 60 50 40 30 20 10 0 FFP 1 : RBC 1 FFP : RBC<1:1
Sperry J: J Trauma 2008;65:986 p = 0,085 p = 0,008 p = 0,001 p = 0,2
Mortality (%) MOF (%) Nosoc. inf (%) ARDS (%)
Con The Relationship of Blood Product Ratio to Mortality: Survival Benefit or Survival Bias?
retrospective analysis in 134 patients the first unit PRBC: median 18 minutes (1 348 min) the first unit of FFP: median 93 minutes (24 350 min)
Therefore, it could be concluded that the nonsurvivors in our study population did not die because they got a lower FFP:PRBC ratio; they got a lower ratio because they died
Snyder C: J Trauma 2009;66 358
Ambiguous
Duchesne et al. J Trauma
2008; 65:2726
Con 1:1
Scalea et al. Ann Surg 2008; 248:57884 Kashuk et al. J Trauma 2008; 65:26170 Snyder C J Trauma 2009; 66:35862
Hirshberg et al. J Trauma 2003; 54:45463 Ho et al. Am J Surg 2005; 190:47984 Gonzalez et al. J Trauma 2007; 62:1129 Borgman et al. J Trauma 2007; 63:805 13 Gunter et al. J Trauma 2008; 65:52734 Maegele M Vox Sang 2008; 95:1129 Cotton et al. J Trauma. 2008;64:117782
Volume expansion and plasma protein clearance during intravenous infusion of 5% albumin and autologous plasma.
Hedin A and Hahn G. Clinical Science 2005;10:217-224
FFP causes volume expansion and dilution no relevant increase in clotting factor concentrations
FFP- effective ?
Is FFP clinically effective? A systematic review of randomized trials. 57 studies: only 5 studies with possible benefit Stanworth SJ BJH 2004 The role of prophylactic FFP in decreasing blood loss and correcting coagulopathy in cardiac surgery A systematic review 6 studies: no effect on blood loss Casbard AC Anaesthesia 2004
Coagulation management with FFP and clotting factor concentrates in severe traumatized patient: CT scan at admission to trauma centre
Coagulation management with FFP and clotting factor concentrates in severe traumatized patient
12 RBC 1 TK 15 FFP FibTEM MCF: 6 mm exTEM MCF: Fibrinogen: 48 mm 232 mg/dL 10 g Fibrinogen 3 mm 27 mm 60 mg/dL 27 mm 61 mm 285 mg/dL
3-fold increase!
Transfusion of FFP Gabe was associated with: VAP with (RR 5.42) and without shock (RR 1.97) septic shock with positive blood culture (RR 3.35) non specified septic shock (RR 3.22) RR for transfusion of FFP and all infections: 2.99 Crit Care Med. 2008 Apr;36(4):1114-1118
Conclusion: no difference in new bleeding episodes new onset acute lung injury was more frequent in the transfused group (18% vs. 4%, p =.021). risk-benefit ratio of FFP transfusion in critically ill medical patients with coagulopathy may not be favorable. Crit Care Med. 2005; 33(11):2667-2671
Each unit of FFP was independently associated with a 2.1% higher risk of MOF and a 2.5% higher risk of ARDS.
Treatment - FFP
Fluid therapy in haemorrhagic shock: Yes! Massive Transfusion Protocols: better than nothing! Target Controlled Bleeding Management?
1. Fibrinogen 2. Prothrombin 3. Factor V 4. Factor VII 5. Platelets Hiippala ST Anesth Analg 1995
critical level of fibrinogen in clinical practice? Charbit B et al.: fibrinogen as an early predictor for severe PPH.
J Thromb Haemost (2007) Gerlach R et al.: postoperative haemorrhage after intracranial surgery and fibrinogen. Stroke (2002) Blome M et al.: fibrinogen and postoperative bleeding in CABG. Thromb Haemost (2005) Ucar HI et al.: Preoperative fibrinogen and postoperative bleeding after open heart surgery. Heart Surg Forum (2007) Karlsson H et al.: plasma fibrinogen level and CABG. Transfusion (2008) Stinger H et al.: high ratio of FI:transfused RBC improved mortality in combat causuality and massive transfusion. J Trauma (2008)
7 5 0 0
I4 T I4 T
5 I T% 4) 5 % ) 0 I T% 4) 0 % ) 5 I T% 4) 5 % ) 2 0 0 m g / d l ( H c t 4 5 2 0 0 m g / d l ( H c t I N I T IT I N I T% 4) 5 % )
5 0 0 0
BL 3.750 ml
2 5 0 0
>2000ml
BL 1.900 ml BL 750 ml
4 0 04 0 0
0 0
1 10 00 0
2 0 2 00 0
3 0 0 3 0 0
F F i ib b P PL LA AS
( M M A A - M- M IN IN S
m g /g d /l d ) l) (m
FI 150 mg/dL: 750 ml or 3.750 ml Critical FI levels may be reached before the need of RBCs!!!
Methods
Observational study in 69 patients Retrospective analysis of 9 children with aquired fibrinogen deficiency Retrospective analysis of 43 patients with aquired fibrinogen deficiency Prospective controlled randomized study in 20 patients Controlled prospective randomized study in 20 patients Controlled prospective randomized study in 18 patients Controlled prospective randomized study in 18 patients
Results
Normalisation of coagulation following fibrinogen concentrate Normalisation of coagulation following fibrinogen concentrate
Normalisation of coagulation and reduced transfusion rate following fibrinogen concentrate Normalisation of coagulation and reduced transfusion rate following fibrinogen concentrate reduced blood loss and transfusion rate following fibrinogen concentrate
reduced blood loss and transfusion rate following fibrinogen concentrate reduced blood loss and transfusion rate following fibrinogen concentrate
recommendation 28: we recommend treatment with FI if significant bleeding is accompanied by TEG signs of functional fibrinogen deficit or a plasma FI level of less than 1.5 2.0 g/l (Grade 1C). We suggest an initial fibrinogen concentrate dose of 3-4g or 50mg/kg. Repeated doses may be guided by TEG monitoring and laboratory assessment (Grade 2C).
Coagulation Management in traumatized and massiv bleeding patients Task Force for perioperative Coagulation (AGPG) of the Austrian Society for Anaesthesia, Critical Care Medicine and Emergency Medicine (GARI)
1. anaemie: 8 9 (10) g/dL. 2. avoid hypothermia, warm infusion solutions, active warming if possible 3. acidosis: buffer therapy, if coagulation therapy is indicated 2. hyperfibrinolysis: consider the use of tranexamic acid in all kind of massive transfusion 3. platelets: > 50.000 100.000 x103l 4. FFP: patients with severe trauma and coagulopathy will not recover from FFP alone; targeted administration of clotting factors is favorable. 5. fibrinogen: > 1,5 g/dL 2,0 g/dL 6. rFVIIa: if surgery, interventional radiology, packing, etc. fails and only after appropriate coagulation therapy. 7. local hemostyptic wound deressings: QuickClot, Hemcon, Combat Gauze, etc. are much more effective than standard gauze dressing