Hydroxyethyl starches (HES)

The high cost of human albumin dictated the development of synthetic colloids. Currently HES are the most commonly used synthetic colloids (Table 22.1). HES are produced by hydroxyl substitution of amylopectin obtained from sorghum, maize, or potatoes. A high degree of substitution on glucose molecules protects against hydrolysis by non-specific amylases in the blood, but the action increases accumulation in liver and spleen macrophages, which constitute the reticuloendothelial system, probably because the reticuloendothelial system recognizes HES as a foreign substance and stores it (in the liver, spleen, and skin).[21] HES administration causes changes in coagulation and fibrinolysis.[22] The effect on fibrinolysis is driven by reduction in alpha2-antiplasmin/plasmin interactions with simultaneous reduction in all measures of coagulation such as clotting time, maximum clot firmness, and alpha-angle; these changes are driven by platelet dysfunction and loss of coagulation factors.[22,23] Growing evidence now questions the safety of traditional and modern HES owing to an increased incidence of mortality and renal failure observed in large randomized controlled trials (RCTs). However, these trials have only focused on critically ill septic patients, and have ignored trauma or cardiac surgical populations. Currently used HESs have a reduced concentration (6%) with a molecular weight (MW) of 130 kDa and a substitution of 0.38–0.45. HES is widely used for patients undergoing anesthesia for major surgery and in patients in ICU.

The raw material from which HES is synthesized is amylopectin (starch). HES is generated by nucleophilic substitution of amylopectin to ethylene oxide in the presence of an alkaline catalyst. Residual solvents are removed by repeated ultrafiltration. HES with a molar substitution of 0.5 or 0.6 is denoted as “pentastarch” or “hexastarch,” respectively. In this regard, first-generation HESs consist of heta- and hexa-starches, whereas pentastarch is allocated to the second generation. The latest, third-generation HESs consist of modern tetrastarches (HES 130/0.4 and HES 130/0.42).

Gelatins

These are prepared by hydrolysis of bovine collagen. Succinylated gelatin (Gelofusine™) is produced by enzymatic alterations of the basic gelatin peptide and is presented in isotonic saline. Urea-linked gelatin (Polygeline, Haemaccel™) is produced by thermal degradation of the raw material to small peptides (12,000–15,000 Da) followed by urea cross-linking to produce polymers of around 35,000 Da that are suspended in isotonic sodium chloride with 5.1 mmol/l potassium and 6.25 mmol/l calcium.[24] Concerns have been raised about association between the use of bovine-derived gelatin (but not pharmaceutically derived), bovine spongiform encephalitis, and Creutzfeld–Jakob disease.[24]

Dextrans

These are biosynthesized from sucrose by Leuconostoc bacteria using the enzyme dextran sucrase. This enzyme catalyzes the alpha-1,6-glycosidic linkage of glucose monomers. Dextrans are defined by their MW, with dextran 40 and 70 having MW 40,000 and 70,000 Da, respectively. Allergic reactions (<0.35%) have been associated with dextrans.[5] Injection of a hapten, dextran 1, before administering dextran solutions has significantly reduced the incidence to <0.0015%.[25] This involves a 20 ml injection of low-MW dextran 1 (1,000 Da MW) prior to infusion of a dextran volume expander, which leads to inactivation of anti-dextran IgGs in the recipient.