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Starches

Created: 23/4/2012
Updated: 14/5/2012

 
In the UK, hydroxyethyl starches (HES) are more commonly used in the intensive care setting. They are a derivative of amylopectin, which if left unmodified would break down too rapidly; therefore, some of the hydroxethyl groups, mainly at C2 and C6, are substituted with anhydroxyethyl glucose groups.“Hydroxyethyl starches are identified by three numbers, e.g. 10% HES 200/0.5 or 6% HES 130/0.4.  The first number indicates the concentration of the solution, the second represents the mean molecular weight (MW) expressed in kiloDalton (kDa), the third and most significant one is the molar substitution (MS).”
These figures effect the pharmacokinetics of the HES, for example 10% HES solutions are hyperoncotic, whereas 6% HES are isooncotic.  The average MW gives the average size of the particles.  Some of the colloid will have a smaller MW and thus will be excreted more rapidly than the larger particles.  As the larger molecules are broken down to smaller molecules they too exert an osmotic effect and in this way they are able to continuously supply the oncotic pressure that is required.  The MS refers to the degree of substitution by the anhydroxyethyl glucose groups.  More substitution means slower degredation and therefore a longer action as indicated by a higher half-life.  The older starches tended to have very long half lives whereas newer starches such as Voluven® and Vitafusal® have a shorter half-life of around 6 hours.
One advantage of using a starch is the longer duration of action as well as the lower cost compared to albumin, although they are more costly than synthetic gelatins.  It is thought they can encourage restoration of cell mediated function and macrophage function after hemorrhagic shock11.  
The first and second generation of starches had the following disadvantages:
A reduction in circulating factor VIII and von Willebrand factor, along with impaired platelet function, prolongation of partial thromboplastin time increasing bleeding complications6
Accumulation in the interstitial spaces and reticulo-endothelial system6 
Anaphylactoid reactions12
A risk of causing renal impairment or acute renal failure in patients who were critically ill with existing renal impairment13-14.
Within the United Kingdom, third generation starches are now more commonly used than the first and second generation starches.  These tetrastarches are derived either from grain or potato.  They generally have a lower molecular weight and therefore have shorter half-lives.  The evidence also points to tetrastarches having fewer side effects than the first and second generation starches, whilst still maintaining their volume expanding efficacy. 
Mitra et al (2009) points out:
“... the more rapidly degradable HES products have been found to have a greatly reduced effect on the coagulation process compared to older products.”
Leuschner et al note a significant reduction in tissue storage of 130/0.4 HES compared to 200/0.5 resulting in a reduction of HES-related pruritus15
The reduced accumulation also seems to decrease the adverse effects on renal function. There are now several studies in both potato and maize based tetrastarches confirming that the newer HES products have no adverse effects on renal function15.

“Hydroxyethyl starches are identified by three numbers, e.g. 10% HES 200/0.5 or 6% HES 130/0.4. The first number indicates the concentration of the solution, the second represents the mean molecular weight (MW) expressed in kiloDalton (kDa), the third and most significant one is the molar substitution (MS).”

[Mitra et al (2009)]

These figures affect the pharmacokinetics of the HES; for example, 10% HES solutions are hyperoncotic, whereas 6% HES are iso-oncotic. The average MW gives the average size of the particles. Some of the colloid will have a smaller MW and thus will be excreted more rapidly than the larger particles. As the larger molecules are broken down to smaller molecules, they too exert an osmotic effect and in this way they are able to continuously supply the oncotic pressure that is required. The MS refers to the degree of substitution by the anhydroxyethyl glucose groups. More substitution means slower degradation and therefore a longer action, as indicated by a higher half-life. The older starches tended to have very long half-lives, whereas newer starches such as Voluven® and Vitafusal® have a shorter half-life of around 6 hours.

One advantage of starch is the longer duration of action as well as the lower cost compared with albumin, although they are more costly than synthetic gelatins. It is thought that they can encourage restoration of cell-mediated function and macrophage function after haemorrhagic shock.

The first and second generation of starches had the following disadvantages:

• A reduction in circulating factor VIII and von Willebrand factor, along with impaired platelet function and prolongation of partial thromboplastin time, increasing bleeding complications.

• Accumulation in the interstitial spaces and reticulo-endothelial system

• Anaphylactoid reactions

• A risk of causing renal impairment or acute renal failure in patients who were critically ill with existing renal impairment.

Within the UK, third-generation starches are now more commonly used than the first- and second-generation starches. These tetrastarches are derived either from grain or potato. They generally have a lower molecular weight and therefore have shorter half-lives. The evidence also points to tetrastarches having fewer side effects than the first- and second-generation starches, while still maintaining their volume expanding efficacy.


“... the more rapidly degradable HES products have been found to have a greatly reduced effect on the coagulation process compared to older products.”

[Mitra et al (2009)]

Leuschner et al note a significant reduction in tissue storage of 130/0.4 HES compared with 200/0.5, resulting in a reduction in HES-related pruritus.

The reduced accumulation also seems to decrease the adverse effects on renal function. There are now several studies in both potato- and maize-based tetrastarches, confirming that the newer HES products have no adverse effects on renal function.


References


[1] National Institute for Clinical Excellence.  TA74 Trauma - fluid replacement therapy: understanding NICE guidance, 28 January 2004.  (Also available from: http://guidance.nice.org.uk/TA74/PublicInfo/pdf/English [accessed 17 April 2012].

[2] Mitra S et al.  Are all colloids same? How to select the right colloid? Indian J Anaesth 2009; 53: 592-607

[3] Schmand JF et al. Effects of hydroxyethyl starch after trauma-hemorrhagic shock: restoration of macrophage integrity and prevention of increased circulating interleukin-6 levels. Crit Care Med 1995; 23: 806-814.

[4] Schortgen F et al. Effects of hydroxyethylstarch and gelatin on renal function in severe sepsis: a multicentre randomised study. Lancet 2001; 357: 911-916.

[5] Davidson IJ.  Renal impact of fluid management with colloids: a comparative review. Eur J Anaesthesiol 2006; 23: 721-738
.
[6] Westphal et al. Hydroxyethyl starches: different products - different effects
Anaesthesiology 2009; 111: 187-202.






ArticleDate:20120423
SiteSection: Article
 

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