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ALL HES ARE NOT THE SAME

Hasanul Arifin

The 2nd Symposium on Critical Care and Emergency Medicine Medan, 30 June 2 July 2006
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HES
(Hydroxyethyl Starch) 6%-10% solution of HES in isotonic saline Preparation mainly from wax corn starch Consist to > 95% of amylopectin (high water binding capacity)

CHARACTERISTIC OF THE SUBSTANCE


Amylopectin consist of a branch chain of glucose molecules Amylopectin easy degradation by -1,4 amylase Substitution (hydroxyethylation) controlled degradation

CHARACTERISTIC OF THE SUBSTANCE


Hydroxyethylation prevents rapid degradation

High degree of substitution = prolonged degradation

HES
450/0.7 200/0.5
degree of substitution 0.5 5 of 10 glucose molecules are substituted by hydroxyethyl groups
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130/0.4

CHARACTERISTIC OF THE SUBSTANCE

HES 130/0.4;11.2 ,6%


Pattern of substitution (C2/C6 ratio) High pattern = prolonged degradation

C6

C2

HES
(Hydroxyl Ethyl Starch)

Hetastarch 1974
Hexastarch 1978 Pentastarch 1980

6% HES
6% HES 6%-10% HES

450/0,7
200/0,62 200/0,5

Tetrastarch 1999

6% HES

130/0,4

Degree of substitution Pattern of substitution

Duration of the volume effect (intravascular half life)

Cleavage by -1,4 amylase

Ensures the continuous supply of osmotically effective molecules from the higher MW

Plateau effect constant volume effect Renal excretion of small molecules (<60-70 kD, leave the intravascular space renal threshold)
v o l time
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Hydroxyethylstarches characteristics
Molecular Weight High Medium Low Substitution Ratio High Low C2/C6 ratio High Low Concentration High Low 450.000 480.000 130.000 200.000 40.000 70.000

0.6 0.7 0.4 0.5


8 < 8 6% 10%
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Hydroxyethylstarches characteristics
Molecular Weight Plasmasteril Elohes Haes-steril Voluven Plasmafusin Expafusin 450.000 200.000 200.000 250.000 130.000 120.000130.000 70.000 Degree of C2/C6 ratio substitution 0.7 0.62 0.5 0.4 0.5 0.5
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In vivo MW (kD)

10 5-6 11.2

140-150 110-120 65

Hydroxyethylstarches characteristics
HES 450/0.7 Concentration (%) MW (daltons) MN (daltons) COP (mmHg) 6 450.000 70.000 24-30 HES 200/0.62/10 6 200.000 60.000 25-30 HES 200/0.5/5 6-10 200.000 70.000 36-68 HES 130/0.4/11.2 6 130.000 68.000 36

Volume effect (%)


Plasma t (h)

100
10-12

110
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100-145
4-8

100
4-6
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HES VOLUME LIMITATION


HES 450/0.7 HES 200/0.62/10 HES 200/0.5/5.1 HES 130/0.4/11.2 20 ml/kg/day 33 ml/kg/first day, 20 ml/kg/day there after 33 ml/kg/day 50 ml/kg/day

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Haemostasis and Coagulation

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Haemostasis and Coagulation


Reduction of factor VIII and von Willebrands factor activity Impairment of platelet function Increases in the APTT

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Interference with haemostasis and coagulation depend on : MW, degree (molar) of substitution and C2/C6 ratio

MW, degree (molar) of substitution and C2/C6 ratio

effect

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HES 450/0.7 will induce more severe effects (haemostasis and coagulation) than the same quantity of a HES 200/0.5 or HES 130/0.4

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HES 200/0.7 will interfere more than HES 200/0.5

HES 200/0.5; 9 will interfere more than HES 200/0.5; 5

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Interference with haemostasis and the potential for severe bleedings is the reason for the limitations of the daily dose of HES

HES 200/0.5 ;6% : up to 2.0 g/kg/d HES 130/0.4 ;6% : up to 3.0 g/kg/d

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Depend on dosing
The incidence of coagulation disorders after administration of rapidly degradable HES solutions with low in vivo MW up to their dosing limits, was reported very low. For these HES solutions (HES 200.0.5 ; HES 130/0.4) clinically relevant bleeding complications have not yet been reported
Treib J , Baron JF et al : An International view of hydroxyethyl starches. Intensive Care Med 25:258-268,1999 22

Molecular weight of hydroxyethyl starch: is there an effect on blood coagulation and pharmacokinetics?
C. Madjdpour1, , N. Dettori1, , P. Frascarolo1, M. Burki2, M. Boll4, A. Fisch5, T. Bombeli3 and D. R. Spahn1,*

Methods.
Thirty pigs were infused with three different HES solutions (20 ml kg1) with the same degree of molar substitution (0.42) but different molecular weights (130, 500 and 900 kD )

Conclusions.
In low-substituted HES, molecular weight is not a key factor in compromising blood coagulation. The longer initial intravascular persistence of high molecular weight low-substituted HES might result in a longer lasting volume effect.
BJA Advance Access originally published online on February 25, 2005 British Journal of Anaesthesia 2005 94(5):569-576; doi:10.1093/bja/aei108 23

Hextend , HES 550/0.7

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Voluven, a Lower Substituted Novel Hydroxyethyl Starch (HES 130/0.4), Causes Fewer Effects on Coagulation in Major Orthopedic Surgery than HES 200/0.5
Olivier Langeron, MD*, Martin Doelberg, PhD , Eng-Than Ang, MD , Francis Bonnet, MD, Xavier Capdevila, MD, PhD||, and Pierre Coriat, MD*

Implications:
Hydroxyethyl starches are common plasma volume expanders, but may interfere with coagulation at large doses. We tested a novel hydroxyethyl starch specification (Voluven; Fresenius Kabi, Bad Homburg, Germany) which was developed to reduce hemostatic interactions while preserving its efficacy in restoring plasma volume in comparison to HAES-steril (pentastarch; Fresenius Kabi) in major orthopedic surgery.
Anesth Analg 2001;92:855-862 2001 International Anesthesia Research Society
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HES AND RENAL FUNCTION

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HES AND RENAL FUNCTION


Hyperoncotic Renal Failure (Moran and Kapsner)

Generation of a high plasma COP wich counteracts the hydrostatic pressure gradient in the glomerulus Avoidance of hyperoncotic colloid solutions

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HES AND RENAL FUNCTION

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Predisposing factors
Age Preexisting or latent renal disease Dehydration High dose colloids for nonsurgical reasons (stroke, claudication, sudden hearing loss, etc)
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Anesth Analg 2003;96:1453-9

Severe cranio-cerebral trauma ( GCS < 5, 24 hour, stable hemodynamic)


HES 130/0.4 - 6% repetitive dose max 70cc/kgBW/day vs HES 200/0.5-6% max 33cc/kgBW/day + albumine up to total dose 70 cc/kgBW/day up to 28 days 33

Result :
HES 130/0.4
Hospital LOS ( days) HES200/0.5+albumine

20.1 ( 15.4) 4/16

22.6 ( 11.8) 3/15

Mortality

Ventilation days
ICU days

9.6 ( 7.8 )
12.7( 11.3)

15.6 ( 6.2)
19.5 ( 9.1)

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Study Conclusions
HES 130/0.4 can safely be used in critically ill cerebral trauma patients over several days at repetitive dose There is still debate about albumine use Premature study termination ( increase incidence of ICP peak in control group ) sample is small ( it was arrange to be 2 x 20 ( actual no 16 vs 15 )

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HES 130/0.4/11.2

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SUMMARY
There are some HES characteristic differences depends on Molar weight, degree of substitution, C2/C6 ratio (pattern of substitution), % concentration Difference characteristic difference effect (volume effect, duration of plateau effect, renal elimination) and side effect (haemostasis, coagulation, renal)

All HES are not the same


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Assalamualaikum, syukran..

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