1. Some colloids are more equal than others: Does our choice matter? Sibylle A. Kozek-Langenecker Evangelic Hospital Vienna www.perioperativebleeding.org sibylle.kozek@aon.at

2. Cochrane Analysis 2011: … no evidence that one colloid solution is more effective or safe than any other …

3. Cochrane Analysis 2011: …hard to see how their continued use can be justified …

4. Why can‘t we see the difference? unjustified end point of mortality only RCTs: methodological limitations understimation of the risks of hypervolemia overestimation of direct costs for colloids inappropriate fluid monitoring & target values inadequate risks-benefits balance

5. Colloidal fluid therapy UNI-MED Verlag AG Bremen – London – Boston 1. Auflage 2009. ISBN 978-3-8374-1184-3 2. edition in English in press

6. Volume efficacy: HES 130 > Gelatin Van der Linden. Review. Can J Anaesth 2006;53:S30-9

7. Kroll et al,. 1983 Effect of 500 ml volume bolus 650 660 700 640 40 320 580 570 280 120 400 0 100 200 300 400 500 600 700 800 End of Infusion30 min60 min120 min HES 200/0.5, 6%Gelatin 3.5%Ringers's Lactate

8. Hot topic: Colloids in critical illness …effects of gelatin on kidney function unclear… … anaphylactic potential, limited volume effect compared with HES…

9. Cardiac & stroke volume … tetrastarch superior to gelatin

10. Cardiac & stroke volume … tetrastarch superior to albumin

11. Anzahl der Patienten mit Vasopressorbedarf Time * 0 2 4 6 8 10 12 136911152025303540455055 Ringers Gelatin Voluven *P<0.05 Palacio F. 2002 Volume Preload (VP) before spinal anaesthesia for caesarean section Tetrastarch was superior: less vasopressor use better HD stability But we WANT to use arterial blood pressure!

12. Volume efficacy HES : Gelatin 1 : 0 Choi. Crit Care Med 1999;27:200-10

13. Microcirculation & inflammation … tetrastarch sustains pulmonary gas exchange…

15. Allison K. J Trauma 1999 Pulmonary function HES superior to gelatin

16. Microcirculation Pulmonary function 6% Tetrastarch : Gelatin 1 : 0

17. HES ≠ HES

18. Schortgen. Lancet 2001; 357: 911-916 ……… 6% hexastarch = independent risk factor

19. Brunkhorst. NEJM 2008; 358: 125-139 VISEP study Efficacy of Volume Substitution and Insulin Therapy in Severe Sepsis ……… 10% pentastarch: accumulation + toxicity

22. Tetrastarch vs. Gelatin in der ICU Schabinski. Intensive Care Med 2009; 35: 1539-47

23. Kidney function …. 6% Tetrastarch : Gelatin …. 0 : 0 Winkelmayer. Kidney Int 2003;64:1046-9 Davidson. Eur J Anaesthesiol 2006;23:721-38 Wiedermann. Intensive Care Med 2004;30:519-20 Wiedermann. Wien Klin Wochenschr 2004;116:583-94 Suttner. Anasthesiol Intensivmed Notfallmed Schmerzther 2004;39:71-7

24. % 0 0.2 0.4 GelatineDextranAlbuminHES Laxenaire. Ann Fr Anaesth Réanim 1994 * 0.345% 0.273% 0.099% 0.058% * Heta- and Pentastarch Anaphylactic reactions after colloids

25. Safety: anaphylaxis HES : Gelatin 1 : 0 Barron. Arch Surg 2004;139:552-63

26. Coagulopathy & bleeding Anesthesiology 2005;103:654. Transfus Altern Transfus Med 2007;9:173. Best Pract Res Clin Anaesth 2009; 23: 225

27. Differences in platelet-coating capacity Deusch. Anesth Analg 2003;97:680 Franz. Anesth Analg 2001;92:1402 *p<0.05 -40 -30 -20 -10 0 10 20 30 40 Mean fluorescence intensity of PAC-1 (% change) salineHES 70HES 130HES 200 * * * * HES 450 * * ADP TRAP

28. Differences between 2 nd and 3 rd HES generation Pooled analysis: tetrastarch versus pentastarch Kozek. Anesth Analg 2008; 107: 382 HES 130/0.4 versus HES 200/0.5 p value Estimated blood loss (mL)-404 [-689; -119]0.006 Drainage loss (mL)-271 [-474; -70]0.009 Calculated RBC loss (mL)-149 [-247; -50]0.003 RBC transfusion volume (mL)-137 [-231; -43]0.004

29. 0 10 20 30 40 50 60 70 80 90 undiluted control oxypolygelatin HES 130 normal saline modified gelatin HES 200HES 450 urea-linked gelatin HES 550 PAC-1 binding to platelets (% gated) # * * # * Thaler. Anaesthesia 2005;60:554-9 Differences in platelet-inhibiting capacity

30. 132 adult patients undergoing cardiac surgery Total Total ICU study drugred blood cell losslength of stay (mg/kg)(ml)(h) Gelatin48.9 ± 14.6 504 ± 327 43 Tetrastarch 48.9 ± 17.2 544 ± 305 24 PN.S.N.S. N.S. Head-to-head comparison: Gelatin versus Tetrastarch Van der Linden. Anesth Analg 2005; 101: 629

31. 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

32. Meta-analysis: Gelatins versus HES Cheng. TATM 2007; 9 (Suppl): 3

33. C unpublished data, 2011 Meta-Analysis: Tetrastarch and gelatine

34. Head-to-head comparison … blood loss similar after tetrastarch and gelatin …

35. Bleeding risk …. tetrastarch : gelatin …. 0 : 0

37. Conclusion dilutional-hyperchloremic acidosis = transient & benign Crit Care 2010;14:325

39. Hinkelmann J / Westphal M 2009 (unpublished data). Effects of potato vs. waxy maize HES on the gut mucosal microcirculation in septic rats n = 2 rats per group Red blood cell velocity (µm/s) 0 200 400 600 800 1000 1200 Sham Stero ISO CLP Stero ISO CLP Tetraspan CLP Volulyte Waxy maize-derived HES and potato-derived HES are not bioequivalent, since there is clear difference in AUC and plasma clearance. Lehmann G, et al. Drugs RD 2007, 8: 229

40. Hot topic: Colloids in pediatric patients … tetrastarch approved in children & best cost-effectiveness and safety profile….

41. Legal aspects HES : GEL 1 : 1 Gelatin no longer approved in USA Daily dose limit for HES in Europe

42. YES …..our choice (on drug, timing and dosing) matters … 6% tetrastarch is more equal than gelatin: efficacy & safety 4:1 Some colloids are more equal than others: Does our choice matter?

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

44. 1 st International ICU-Thromboprophylaxis Day 2.12.2011 in Vienna Risk factors & thromboprophylaxis - guidelines & current practice Anticoagulation despite bleeding risks Anticoagulation during extracorporeal circulation Monitoring issues Future perspective www.clotwork.at

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

46. Exposure to colloids and clinical outcome: Which comparison is correct? 1.Macrocirculation: volume efficacy of gelatin 4% > tetrastarch 6% 2.Allergic reactions: frequency after albumin > gelatins 3.Renal failure: old HES ≥ 6% is safer than newer tetrastarch 6% 4.Blood loss after tetrastarch is less than after pentastarch ☺