Hydroxyethyl starch

Absorption

Peak concentration (C(max), 4.34 mg/mL)

Toxicity

LDF50 (IV, rabbit): 8460 mg/Kg.

Description

Hydroxyethyl starch (HES) is a synthetic colloid that consists of hydroxyethylated polymers of glucose, derived from amylopectin. It is one of the most frequently used plasma substitutes. HES products are approved for the treatment of hypovolemia (low blood volume).

Chemical properties

White to light yellow powdery solid, non-toxic and odorless. It is easily soluble in water and insoluble in organic solvents. It has properties such as emulsification, dispersion, suspension, and adhesion, and can be used as an aid in filtration and retention of pulp materials. It can also reduce the chemical oxygen demand and biochemical oxygen demand of wastewater.

The Uses of Hydroxyethyl starch

Hetastarch, with a trade name of Hespen, is used widely as volume expanders. An intravenous solution of hydroxyethyl starch is used to prevent shock following severe blood loss caused by trauma, surgery, or other problems.

What are the applications of Application

Hydroxyethyl starch is a substituted starch

Indications

An intravenous solution of hydroxyethyl starch is used to prevent shock following severe blood loss caused by trauma, surgery, or other issues.

Background

Hydroxyethyl starch (HES/HAES) is a nonionic starch derivative. Hydroxyethyl starches (HES) are synthetic colloids commonly used for fluid resuscitation to replace intravascular volume. HES is a general term and can be sub-classified according to average molecular weight, molar substitution, concentration, C2/C6 ratio and Maximum Daily Dose.

Background

Pentastarch is an artificial colloid (hydroxyethyl starch derivative). Pentastarch is characterized by presenting five hydroxyethyl groups, which signifies an approximate 50% hydroxyethylation. It is sold under the name Pentaspan by Bristol-Myers Squibb and is used for fluid resuscitation. When administered, pentastarch remains mainly in the circulatory system and hence, it is considered a plasma expander.

Indications

The primary intended use of pentastarch is as a substitute for older colloids such as albumin or hetastarch for use in plasma volume expansion.

Preparation

Hydroxyethyl starch is produced by the hydroxyethylation reaction of hydrolyzed starch with ethylene oxide and sodium hydroxide.

brand name

Pentaspan (DuPont Merck).

General Description

Hydroxyethyl starches (HES) are nonionic starch derivatives and were one of the most frequently used intravascular volume expanders.

Biochem/physiol Actions

Analysis of cDNA clones indicates that ribosome binding protein 1 may exist in different forms due to removal of tandem repeats, or partial intraexonic splicing of RRBP1. The form presented here is lacking the canine p180 ribosome-binding domain, NQGKKAEGAQ, which is tandemly repeated close to the N-terminus in other forms that haven′t been fully characterized. RRBP1 has been excluded as a candidate gene in the cause of Alagille syndrome. Alternate splicing results in multiple transcript variants. [provided by RefSeq]

Pharmacokinetics

After isovolemic exchange of blood with 500 mL of HES in healthy volunteers, blood volume is maintained for at least 6 hours

Clinical Use

Hydroxyethyl starch is often used as a plasma substitute for therapy of hypovolemia after trauma, burns, infections or during surgery.It is also widely used for hemodilution treatment of cerebral ischemia and of retinal, otogenic or peripheral perfusion disturbances.In treatment of cerebral ischemia, a hypervolemic therapy protocol has been shown to be more effective than an isovolemic infusion. Another indication is the hyperdynamic treatment of vasospasm in subarachnoid hemorrhage.Some of these indications require relatively high dosages to ensure efficacy of therapy.However, during continuous treatment with large volumes of HES, disturbances of coagulation and hemor- rhagic complications are not uncommon. Trumble et al. reported bleeding complications during hetastarch therapy of vasospasm in subarachnoid hemorrhage patients and recommended the use of plasma protein fraction instead.Van den Brink observed coagulopathy under therapy with highly sub- stituted medium molecular weight HES.These disturbances of the coagulation sys-tem were found to be due to an acquired von Willebrand syndrome.

Side Effects

Most of the serious adverse effects reported, such as kidney injury and coagula- tion abnormalitics,have been observed in human studies and have not been docu- mented with clinical use in veterinary medicine.The use in people has become controversial and caution is advised when using these products in animals,with attention to the most commonly reported problems in people.Hetastarch may cause allergic reactions and hyperosmotic kidney injury.Hydroxyethyl starch solu- tions may affect platelet function and produce coagulation abnormalitics at clini- cally relevant doses for up to 24 hours.The high-molecular-weight hetastarch may alter coagulation and alter viscoelastic measurements and fibrinolysis.Do not use in patients with bleeding problems or preexisting coagulopathies. High-molecular- weight products (10% solutions) have molecular weight more than 200 kDa (kilodaltons)and are associated with higher risk of kidney injury.Tetrastarch solu- tions also may have less tendency to cause coagulopathics than hetastarch.There- fore the current recommendation is to use tetrastarch solutions of 6% and reduced molecular weight(130 kDa).

Metabolism

When given intravenously, molecules smaller than the renal threshold (60,000-70,000 daltons) are readily and rapidly excreted in the urine, while molecules with higher molecular weights are metabolized by plasma α-amylase prior to excretion via the renal route.

Metabolism

Pentastarch is hydrolyzed by plasma amylase. This is more rapid and complete compared to hetastarch.

Metabolism

Ten volunteers were given 500 ml 6% HES solution by intravenous infusion, and serial blood and urine samples were collected for nonglucose total carbohydrate determination. On average, 46 and 64 percent of the dose was excreted in the urine within two and eight days. The plasma concentration declined rapidly during the first week after infusion. The average terminal half-life was 17 days during the first 42 days, which accounted for the elimination of about 90 percent of the dose. The remainder was eliminated with a terminal half-life of 48 days determined between days 42 and 83 of the study. The infusion of HES resulted in plasma volume expansion over a 48-hour when nonglucose carbohydrates were above 3.5 mg/ml. HES is metabolized by alpha-amylase in the body. During the first 48 hours after infusion of HES, plasma alpha-amylase activity was significantly increased over control. Concomitantly, alpha-amylase activity in urine was also elevated but not significantly so[1].

References

[1] Yacobi, A et al. “Pharmacokinetics of hydroxyethyl starch in normal subjects.” Journal of clinical pharmacology vol. 22,4 (1982): 206-12. doi:10.1002/j.1552-4604.1982.tb02164.x