IFAD 2011

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
580570
280
120
400400
0
100
200
300
400
500
600
700
800
End of Infusion 30 min 60 min 120 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
1 3 6 9 11 15 20 25 30 35 40 45 50 55
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
Gelatine Dextran Albumin HES
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
0
10
20
30
40
50
60
70
80
90
0% 1% 3% 5% 10% 20% 40%
hemodilution
FITC-positiveplatelets(%gated)
*
*
*
Franz. Anesth Analg 2001;92:1402
*p<0.05
-40
-30
-20
-10
0
10
20
30
40
Meanfluorescenceintensityof
PAC-1(%change)
saline HES 70 HES 130 HES 200
*
*
* *
HES 450
*
*
ADP TRAP

28. ferences between 2nd
and 3rd
HES generation
oled 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
90undiluted
control
oxypolygelatinH
ES
130
norm
alsaline
m
odified
gelatinH
ES
200H
ES
450urea-linked
gelatinH
ES
550
PAC-1bindingtoplatelets(%gated)
#
*
*
#
*
Thaler. Anaesthesia 2005;60:554-9
Differences in platelet-inhibiting capacity

30. 132 adult patients undergoing cardiac surgery
Total Total ICU
study drug red blood cell loss length of stay
(mg/kg) (ml) (h)
Gelatin 48.9 ± 14.6 504 ± 327 43
Tetrastarch 48.9 ± 17.2 544 ± 305 24
P N.S. N.S. N.S.
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
MCF blood loss
HS-HES 11 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 = 0.0034 p =0.004
Small volume resuscitation

32. Meta-analysis: Gelatins versus HES
Cheng. TATM 2007; 9 (Suppl): 3
Review : Colloids
Comparison: 87 Blood Loss, HES v GEL
Outcome: 01 Blood Loss during Study Period, HES v GEL, mL
Study HES GEL WMD (fixed) Weight WMD (fixed)
or sub-category N Mean (SD) N Mean (SD) 95% CI % 95% CI
01 0.4 and below
Boldt 01 HES 0.4 GEL 25 590.00(210.00) 25 790.00(210.00) 18.92 -200.00 [-316.42, -83.58]
Boldt 03 HES0.4 GEL 20 980.00(230.00) 20 1050.00(250.00) 11.57 -70.00 [-218.88, 78.88]
Haisch 01 HES0.4 GEL 21 740.00(250.00) 21 690.00(220.00) 12.64 50.00 [-92.43, 192.43]
Haish Abd HES0.4 GEL 21 480.00(250.00) 21 580.00(290.00) 9.56 -100.00 [-263.76, 63.76]
Subtotal (95% CI) 87 87 52.69 -93.34 [-163.10, -23.58]
Test for heterogeneity: Chi² = 7.22, df = 3 (P= 0.07), I² = 58.4%
Test for overall effect: Z = 2.62 (P= 0.009)
02 Above 0.4
Boldt 00 HES 0.5 GEL 100 1275.00(640.00) 50 1230.00(440.00) 8.38 45.00 [-129.95, 219.95]
Boldt 01 HES0.5 GEL 25 680.00(230.00) 25 790.00(210.00) 17.20 -110.00 [-232.09, 12.09]
Boldt 92 HES0.5 GEL 12 550.00(210.00) 12 560.00(220.00) 8.66 -10.00 [-182.08, 162.08]
Innerh 02 HES0.5 GEL 20 656.00(269.00) 20 611.00(270.00) 9.19 45.00 [-122.04, 212.04]
Karout 99 HES0.6 GEL 15 821.00(374.00) 15 1064.00(385.00) 3.48 -243.00 [-514.63, 28.63]
MortelmansHES0.5 GEL 21 3437.00(1578.00) 21 2778.00(956.00) 0.41 659.00 [-130.10, 1448.10]
Subtotal (95% CI) 193 143 47.31 -37.23 [-110.84, 36.39]
Test for heterogeneity: Chi² = 8.44, df = 5 (P= 0.13), I² = 40.7%
Test for overall effect: Z = 0.99 (P= 0.32)
Total (95% CI) 280 230 100.00 -66.79 [-117.43, -16.15]
Test for heterogeneity: Chi² = 16.83, df = 9 (P= 0.05), I² = 46.5%
Test for overall effect: Z = 2.59 (P= 0.010)
-1000 -500 0 500 1000
Favours HES Favours GEL

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
Redbloodcellvelocity(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. 1st
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☺