Etherified starches

Definition Starch etherified with propylene oxide, rendering it more resist, to thermal degradation and bacterial attack... 

Star-branched butyl rubber, 4 437-438 copolymers, 4 445-446 Starch(es), 4 703-704, 20 452-453 as blood substitute, 4 111-112 cationic, 18 114-115 in cereal grains, 26 271-274 in cocoa shell from roasted beans, 6 357t compression effects in centrifuges, 5 513 depolymerization, 4 712 in ethanol fermentation, 10 534—535 etherified, 20 563 as a flocculant, 11 627 high-amylose, 26 288 Mark-Houwink parameters for, 20 558t modified and unmodified, 12 52-53 in paper manufacture, 18 122-123 performance criteria in cosmetic use, 7 860t... 

The etherified starch was further transformed by hydrogenation of the double bonds to yield the corresponding linear octyl groups using [RhCl(TPPTS)3] catalyst soluble in EtOH-H20 mixtures. Complete hydrogenation was obtained at 40 °C under 30 bar of H2 after 12 h using 0.8-wt.% Rh-catalyst [84]. Other catalytic transformations such as double bond oxidation and olefin metathesis could possibly be used to prepare other modified starches for various applications. 

There are also patents on compositions of starch with modified esterified, etherified, and cross-linked starch to produce sizes1061 and adhesives.1062-1064... 

The choice of crystalloid or colloid for fluid resuscitation remains controversial. There have been no prospective, randomised trials of sufficient power in either sepsis or trauma, to detect a significant difference in mortality. Albumin is relatively expensive and offers no advantage over cheaper, synthetic colloids such as etherified starch. 

Etherified starch. Several hydroxyethyl starch solutions are available, with widely differing effects on plasma volume. The high molecular weight (450 000) solutions have a volume restoring effect for 6-12 h, while that of medium molecular weight (200 000) starches last 4-6 h. 

A 24-year-old healthy volunteer was given 10 ml of 6% dextran 60 during a preliminary examination (24). After about 5 minutes the first clinical symptoms of anaphylactic shock were evident, with a reduction in systolic blood pressure to 90 mmHg and an increased heart rate to over 90/minute. These returned to normal after therapy in the head-down position with clemastine 2 ml (2mg), hydrocortisone 200 mg, and etherified starch 500 ml over about 8 minutes. During this period, responsiveness was unsatisfactory although he complained of warming of the skin, paresthesia, and nausea. 

Etherified starches are synthetic colloids containing over 90% amylopectin, a waxy starch derived from maize, that has been variably etherified. There are two major forms, hetastarch and pentastarch (both BAN and USAN). They are produced synthetically by introducing hydroxyethyl groups into glucose units of starch molecules, followed by acid hydrolysis, which results in a product with a molecular weight of several thousands of daltons. In hetastarch 7 or 8 and in pentastarch 4 or 5 of the hydroxyl groups in each glucose molecule are etherified. 

The etherified starches are used in solution as plasma substitutes. They are good alternatives to albumin, because they have an extended shelf-life, carry no risk of transmitting blood-borne diseases, and can be infused into patients who refuse blood products on religious grounds. 

The elimination of etherified starches is complex and related to the size of the particles. The smaller molecules, with a molecular weight of less than 50 000 daltons, are excreted unchanged by glomerular filtration. The larger molecules are metabolized to smaller molecules and distributed to various body tissues, where they may undergo hydrolysis in the reticuloendothelial system or enzymatic degradation by amylases. 

Different types of etherified starch are designated by a number that indicates the molecular weight in kilodaltons followed by a number that indicates the degree of substitution of glucose units with hydroxyethyl groups. Thus, etherified starch with a molecular weight of 200 kDa and 62% substitution is designated 200/0.62. 

Some authors have concluded that etherified starches and albumin do not differ with respect to efficacy and adverse effects on coagulation and renal function (3), but etherified starches clearly do have a distinct adverse reactions profile. Some of the problems that they cause, such as anaphylaxis, volume overload, cerebral hemorrhage, and acute renal insufficiency, are sufficient reason to avoid hetastarch when benefit is doubtful, such as ischemic brain infarction (4). 

In a comprehensive comparison of the pharmacokinetics and pharmacodynamics of dextran and etherified starch (8), the effects of etherified starch on the cardiovascnlar system have been delineated. The mean arterial pressnre, central venous pressure, wedge pressure, cardiac index, left ventricular stroke work index, and stroke output aU rise, whereas the pulmonary vascular resistance falls. Oxygen availability to the tissues is improved. The effects of etherified starch on blood viscosity and erythrocjde aggregation, in particular, are more pronounced than with dextran. 

The effect of hemodilution with colloids on somatosen-sory-evoked potentials in non-premedicated volunteers has been reported (9). In seven subjects, blood (20 ml/kg within 30 minutes) was removed and simultaneously replaced by gelatine 3% or etherified starches 6%. After 30 minutes, blood was retransfused. Median and posterior tibial nerve somatosensory-evoked potentials were recorded from the cortex, second cervical vertebra, Erb s point, and first lumbar vertebra. Hemodilution with gelatine or etherified starches or retransfusion did not affect somatosensory-evoked potentials, provided normovolemic conditions were maintained. 

The pathogenic mechanism that affects factor VIII/ vWF complex has not been elucidated. There may be accelerated elimination after attachment of factor VIII/ vWF complex to starch molecules. The significant fall in factor XI and factor XII shows that impairment of the intrinsic system of coagulation is not limited to factor VII/ vWF complex (14). Even a small volume of 6% etherified starches (average molecular weight 450 kDa 2.5 litres in 3 days) can cause a significant coagulation disorder (15). 

This case is typical of many others. In six patients with cerebral circulatory disturbances who received hemodilution therapy for 9-10 days with etherified starches (molecular weight 200 kDa and a high degree of substitution, 0.62), all the multimers of von Willebrand factor fell to the same extent. This corresponds to type 1 von... 

Etherified starch shortens the thrombin time by a fibrinoplastic effect. This accelerates the conversion of fibrinogen to fibrin, resulting in a less stable thrombus, which is more susceptible to lysis. The macromolecules in etherified starch induce an acquired von Willebrand s syndrome with reduced concentrations of aU three main forms of factor VIII factor VIILC, von WiUebrand factor, and von WiUebrand factor antigen (vWFag). 

Plasma substitutes in general reduce the platelet count partly by a dilutional effect, even after a single dose. However, there are other mechanisms. In a study of the effects on platelet number and function of etherified starches, given for 10 days to 20 patients with cerebrovascular diseases, both medium- and low-molecular weight etherified starches caused a significant reduction in the number of platelets on the first day, in excess of a... 

Macromolecules may coat the outer membrane of circulating platelets and cause a quaUtative functional defect, thus prolonging bleeding time. Minor abnormalities of platelet aggregation have been observed after infusion of low volumes of etherified starches, and platelet defects probably contribute to the hemorrhagic state. 

Two cases of osmotic nephrosis-hke lesions have been reported in which similar changes have been noted, accompanied by evidence of renal insufficiency. The first case occurred after the administration of etherified starch during surgery (26). 

The authors suggested that the renal insufficiency was due to the perioperative infusion of etherified starch, even though she received a much smaller dose (less than 10 ml/kg) than kidney donors usually receive. They further suggested that nephrotoxicity can occur within a few hours after even low-dose infusion of etherified starches. 

The authors concluded that the most likely cause of renal insufficiency was etherified starch-induced tubulopathy and hypothesized that even low amounts of etherified starch as replacement fluid in plasma exchange can cause renal tubular lesions in patients predisposed for other reasons (such as drugs or renal hypoperfusion) to renal insufficiency. In this context, albumin should be combined with replacement fluids other than etherified starch. 

Conclusions have differed as to whether use of etherified starch in brain-dead organ donors influences kidney graft function at 1, 3, and 6 months after transplantation (30-32). In one report (33), during the first 10 days after transplantation there was reduced kidney graft function... 

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