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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)
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
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
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
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
100
10-12
110
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100-145
4-8
100
4-6
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Interference with haemostasis and coagulation depend on : 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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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
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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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Generation of a high plasma COP wich counteracts the hydrostatic pressure gradient in the glomerulus Avoidance of hyperoncotic colloid solutions
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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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Result :
HES 130/0.4
Hospital LOS ( days) HES200/0.5+albumine
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)
Assalamualaikum, syukran..
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