1. Towards the perfect fluid strategy: Fluid strategy in hemorrhagic shock Sibylle A. Kozek-Langenecker Evangelic Hospital Vienna www.perioperativebleeding.org sibylle.kozek@aon.at

2. Honoraria for lectures and travel reimbursement: B. Braun Fresenius Kabi Conflicts of interest

3. Severe bleeding: > 20% blood volume loss Massive bleeding: > 100% blood loss in 24 h > 50% blood loss in 3 h > 150 ml/min in 20 mins > 1.5 ml/kg/min in 20 mins > 6 U PRBC in 24 h Martinowitz. J Thromb Haemost 2005; 3: 640 Definition: hemorrhage

4. Na + K+K+ K+K+ intravascular interstitial intracellular Na + K+K+ protein water protein Physiological basics

5. mod. Jacob 2012

6. 45 litres

7. intracellular space 30 litres

8. 15 litres extracellular space

9. 12 litres interstitial space

10. 3 litres intravascular space

11. Pathophysiological basics in hemorrhagic shock: intravascular compartment tissue perfusion in hemorrhagic shock: intravascular compartment tissue perfusion

12. Fluid strategy in hemorrhagic shock in hemorrhagic shock: stopp bleeding intravascular compartment tissue perfusion

13. infusion therapy fluid volume substitution replacement extracellular intravascular crystalloid colloid Physiology-based fluid strategy in hemorrhagic shock AND

14. pure water Pharmacodynamics

15. isotonic crystalloid Pharmacodynamics

16. urine output extravascular deficits insensible perspiration evaporation Fluid substitution Lamke. Acta Chir Scand 1977; 143: 279-84 Jacob M, Chappell D, Rehm M. Lancet 2007; 369: 1984-6 0.5-1 ml/kg/h

17. Excessive crystalloid substitution Jacob. Anaesthesist 2007, 56:747-64 Hypervolemia

18. Keep the glycocalyx happy ☺ Chappell 2008 Chappell D. Cardiovascular Research 2009; 83:388–396

19. isooncotic colloid Pharmacodynamics

20. Volume efficacy Van der Linden. Review. Can J Anaesth 2006;53:S30-9

21. Direct measurement of volume efficacy Proof of concept: isooncotic colloids act intravascular

22. Context-sensitivity of volume efficacy in hemorrhagic shock: highest volume efficacy Jacob. Lancet 2007, 369: 1984-6

23. Context-sensitivity on the cover

24. Tissue trauma + Consumption Tissue trauma + Hyperfibrinolysis Cut vesicles Pre-existing disorders Anticoagulation Antiplatelet drugs Blood loss Fluid resuscitation + Dilution Triad of Malfunction (hypothermia, acidosis, hypocalcaemia) Pathomechanisms of massive bleeding Kozek. In: Yearbook of Intensive Care and Emergency Medicine 2007:847 Thrombomodulin / Protein C

25. Dilutional coagulopathy baseline hemodilution Fries. Anesth Analg 2002; 94:1280 Innerhofer. Anesth Analg 2002; 95: 858 reversal

26. The ideal intravascular resuscitation fluid good volume efficacy no coagulopathic side effect no other relevant side effects

27. 1:1:1 ratio concept: á 600 ml 500 mL Hct: 38- 45% Plt: 150- 400K Coags: 100% PRBC Hct 55% 335 mL Plt 5.5x10 1 0 50 mL FFP 80% 250mL 1U PRBC + 1U PLT + 1U FFP: factor activity 65% Platelet count 87K Hct 29% Armand & Hess. Transfusion Med Rev 2003 volume efficacy ? coagulopathy ? harms/burdens ?

28. Schöchl. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine 2012; 20: 15 Minerva Anestesiol 2005 JSTEM 2012 Concentrate-based concept: á 50 ml

29. Dosing of fluids target parameters & safety aspects

30. Acidosis ≠ acidosis Gunnerson. Crit Care 2006; 10:R22

31. Fluids In Resuscitation in Severe Trauma James. Br J Anaesth 2011;107:693 The FIRST Study: Lactate clearance similar static hemodynamic measurements between groups superior tissue perfusion after HES

32. ESA guideline 2012Management of severe periOP bleeding 9-10 of November 2012 Prague, Czech Republic

33. Colloidal patient safety issues overload endothelial damage intraabdominal hypertension dose of colloid „therapeutic window“ inadequate volume therapy death anaphylaxis coagulopathy & bleeding kidney dysfunction itching adverse outcomes

34. Colloidal safety measures individualized dosing IA pressure monitoring ? dose of colloid „therapeutic window“ fluid monitoring and individualised dosing anamnesis, awareness & symptomatic treatment Choice of colloid avoidance of adverse outcomes

35. Potential side effects of colloids - Coagulopathy beyond hemodilution Anesthesiology 2005;103:654. Transfus Altern Transfus Med 2007;9:173. Best Pract Res Clin Anaesth 2009; 23: 225

36. Side effects on hemorrhage dextran > pentastarch > tetrastarch/gelatins ~ albumin maximum daily dose in massive bleeding ?

37. Haas. Anesth Analg 2008;106:1078 30 pigs after 60% blood volume withdrawal intervention: 4 ml/kg hypertonic saline (7.2%) / HES (6% 200/0.62) 50 ml/kg 4% gelatin 41 ml/kg 6% tetrastarch MCFblood loss HS-HES11 mm (10,11)725 ml (375, 900) tetrastarch 3.5 mm (2.3,4)1600 ml (1500,1800) gelatin 4.5 mm (3,5.8)1625 ml (1275,1950) p = 0.0034p =0.004 Small volume resuscitation

38. Small volume resuscitation & outcome shock + blunt/penetrating trauma: no difference in mortality BUT increased mortality in subgroup without RBCs Bulger EM. JAMA. 2010; 304:1455-64 shock + traumatic brain injury: no difference in mortality and neurological outcome Cooper D. JAMA 2004; 291;1350-1357

39. heterogeneous fluid/procoagulant concepts exist in a pathophysiology-based infusion concept: fluid substitution: balanced isotonic crystalloids volume replacement: isooncotic colloids hemodynamic monitoring: preload & metabolic parameters > HR & pressure parameters avoid hypervolemia monitoring of colloidal side effects:dependent on molecule, dosing, timing, endothelial barrier Conclusions

40. FRACTA 2013 February 7 th -9 th 2013 in Prague safe the date sybille.richter@fresenius-kabi.com

41. www.perioperativebleeding.org sibylle.kozek@aon.at Thank you for your attention !