Etherified starches

Nomenclature

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.

General adverse effects and adverse reactions

Transitory hyperamylasemia, chills, and mild increases in body temperature, pruritus, enlargement of the submandibular and parotid glands, and erythema multiforme can occur [ ]. The risk of anaphylactic reactions to hetastarch is very small (about 5 per million) [ ].

Comparative studies

The efficacy and safety of hetastarch and albumin have been compared in 85 patients with postaneurysmal subarachnoid hemorrhage [ ]. Of 26 patients who developed clinical symptoms of vasospasm, 14 were treated with hetastarch, while the other 12 received albumin. In all patients who received hetastarch there was significant prolongation of the partial thromboplastin time after transfusion (pretransfusion mean 24 seconds, post-transfusion 33 seconds), while in patients treated with albumin the partial thromboplastin time was not significantly altered. The prolongation of the partial thromboplastin time resulted in increased occult blood loss in the hetastarch-treated patients, requiring blood transfusion in four patients. On the basis of hetastarch-associated coagulopathy and data that show that albumin may be the most effective agent for increasing cerebral blood flow and preventing infarction, the authors stopped using hetastarch in these patients and decided to recommend albumin exclusively.

Some authors have concluded that etherified starches and albumin do not differ with respect to efficacy and adverse effects on coagulation and renal function [ ], 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 [ ].

The effects of different volume expanders on cardiac output in a neonatal population with hemodynamic failure have been compared in a randomized clinical trial [ ]. Hydroxyethyl starch is not more efficacious than isotonic saline or albumin. There were no adverse effects related to fluid resuscitation.

Placebo-controlled studies

Hypervolemic hemodilution with agents such as etherified starches or dextran increases cerebral blood flow and can therefore reduce ischemic tissue damage in the penumbra zones when given within the therapeutic time window. However, the clinical benefit of such therapy has yet to be proven. Since etherified starch is considered to be the safer choice, in particular the recently developed lower molecular weight form (etherified starch 130/0.4), an explorative, randomized, placebo-controlled, safety trial of etherified starch for hypervolemic hemodilution in patients with acute ischemic stroke has been undertaken [ ]. This was a double-blind, randomized, placebo-controlled, parallel-group, multicenter study in 106 patients with acute ischemic stroke, who were recruited over 3 years. Treatment comprised high-dose hypervolemic hemodilution with either etherified starch 130/0.4 or placebo within 6 hours of the start of symptoms, with a randomization ratio of 2:1 in favor of etherified starch. There were no significant differences between the groups with regard to the incidence of specific adverse events (cardiovascular, bleeding complications, allergic reactions), assessed over days 1–30, or of deaths over days 1–8. The author, on behalf of the Hydroxyethyl Starch in Acute Stroke Study Group in Germany, noted that while the study was not designed to prove efficacy, the global tests of efficacy suggested a slight but insignificant trend toward better functional outcome with etherified starch.