7.3: Colloids

Colloids are large molecular weight (nominally MW > 30,000) substances. In normal plasma, the plasma proteins are the major colloids present. Colloids are important in capillary fluid dynamics because they are the only constituents which are effective at exerting an osmotic force across the wall of the capillaries. Albumin solutions are available for use as colloids. In addition, various other solutions containing artificial colloids are available. The general problems with colloid solutions are:

• much higher cost than crystalloid solutions
• small but significance incidence of adverse reactions (esp anaphylactoid reactions)

7.3.1: Molecular Weight

Two molecular weights are quoted for colloid solutions (see Huskisson 1992 for definitions):

• Mw : Weight average molecular weight
• Mn : Number average molecular weight

The Mw determines the viscosity and Mn indicates the oncotic pressure. Albumin is said to be monodisperse because all molecules have the same molecular weight (so \(Mw = Mn\)). Articial colloids are all polydisperse with molecules of a range of molecular weights.

7.3.2: The Ideal Colloid Solution

The properties of an ideal colloid solution for use as a plasma volume expander are outlined in the table. An oncotic pressure similar to plasma will permit replacement of plasma volume without distribution to other fluid compartments and this is the key element that makes a solution a colloid solution.

Table 7.3: The Properties of an Ideal Colloid

General

Distributed to intravascular compartment only Readily available Long shelf life Inexpensive No special storage or infusion requirements No special limitations on volume that can be infused No interference with blood grouping or cross-matching Acceptable to all patients & no religious objections to its use

Physical Properties

Iso-oncotic with plasma Isotonic Low viscosity Contamination easy to detect

Pharmacokinetic Properties

Half-life should be 6 to 12 hours Should be metabolised or excreted & not stored in the body

Non-Toxic & No Adverse Affect on Body Systems

No interference with organ function even with repeated administration Non-pyrogenic, non-allergenic & non-antigenic No interference with haemostasis or coagulation Not cause agglutination or damage blood cells No affect on immune function including resistance to infection No affect on haemopoiesis Not cause acid-base disorders Not cause or promote infection (bacterial, viral or protozoal)

7.3.3: Dextrans

Dextrans are highly branched poysaccharide molecules which are available for use as an artificial colloid. They are produced by synthesis using the bacterial enzyme dextran sucrase from the bacterium Leuconostoc mesenteroides (B512 strain) which is growing in a sucrose medium.

The formulations currently available are:

Dextran 40 (Mw 40,000 & Mn 25,000) [Rheomacrodex]

Dextran 70 (Mw 70,000 & Mn 39,000) [Macrodex].

The dextrans cause more severe anaphylactic reactions than the gelatins or the starches. The reactions are due to dextran reactive antibodies which trigger the release of vasoactive mediators. Incidence of reactions can be reduced by pretreatment with a hapten (Dextran 1).

Dextran 70 has a duration of action of 6 to 8 hours. Interference with crossmatching occurs so the laboratory should be notified that dextrans have been used. Dextran interferes with haemostasis; it induces an acquired von Willebrand's state. Consequently, there is a maximal dosage recommendation of 20 mls/kg (about 1,500 mls in an adult).

Dextran40 is used to improve microcirculatory flow in association with certain procedures (eg microsurgical reimplantations).

7.3.4: Gelatins

Gelatin is the name given to the proteins formed when the connective tissues of animals are boiled. They have the property of dissolving in hot water and forming a jelly when cooled. Gelatin is thus a large molecular weight protein formed from hydrolysis of collagen.

Gelatin solutions were first used as colloids in man in 1915. The early solutions had a high molecular weight (about 100,000). This had the advantage of a significant oncotic effect but the disadvantages of a high viscosity and a tendency to gel and solidify if stored at low temperatures. Reducing the molecular weight reduced the tendency to gel but smaller molecular weight molecules could not exert a significant oncotic effect. The need was for a modified gelation product that had a moderate molecular weight (for oncotic pressure) but a low gel melting point. (It is difficult to infuse a jelly).

Several modified gelatin products are now available; they have been collectively called the New-generations Gelatins. There are 3 types of gelatin solutions currently in use in the world:

• Succinylated or modified fluid gelatins (eg Gelofusine, Plasmagel, Plasmion)
• Urea-crosslinked gelatins (eg Polygeline)
• Oxypolygelatins (eg Gelifundol)

Polygeline (Haemaccel Hoechst) is available in Australia. The gelatin is produced by the action of alkali and then boiling water (thermal degradation) on collagen from cattle bones. The resultant polypeptides (MW 12,000 - 15,000 ) are urea-crosslinked using hexamethyl di-isocyanate. The branching of the molecules lowers the gel melting point. The MW ranges from 5,000 to 50,000 with a weight-average MW of 35,000 and a number-average MW of 24,500.

Properties

Polygeline is supplied as a 3.5% solution of degraded gelatin polypeptides cross-linked via urea bridges with electrolytes (Na⁺ 145, K⁺ 5.1, Ca²⁺ 6.25 & Cl^- 145 mmol/l). It is sterile, pyrogen free, contains no preservatives and has a recommended shelf-life of 3 years when stored at temperatures less than 30°C.

Handling by the Body

It is rapidly excreted by the kidney. Following infusion, its peak plasma concentration falls by half in 2.5 hours. Distribution (as a percent of total dose administered) by 24 hours is 71% in the urine, 16% extravascular and 13% in plasma The amount metabolised is low: perhaps 3%.

Indications

The major use of Polygeline is the replacement of intravascular volume eg correcting hypovolaemia due to acute blood loss. It is also used in priming heart-lung machines.

Advantages

• Lower infusion volume required as compared to crystalloids
• Cheaper and more readily available then plasma protein solutions
• No infection risk from the product if stored and administered correctly
• Only limit to the volume infused is the need to maintain a certain minimum [Hb] (In comparison, dextrans have a 20ml/kg limit).
• Readily excreted by renal mechanisms
• Favourable storage characteristics: long shelf life, no refrigeration
• No interference with blood cross-matching
• Compatible with other IV fluids except Ca²⁺ can cause problems with citrated blood products.

Disadvantages

• Higher cost then crystalloids
• Anaphylactoid reactions can occur
• No coagulation factors and its use contributes to dilutional coagulopathy

Starches

These polydisperse colloid solutions are produced from amylopectin which has been stabilised by hydroxyethylation to prevent rapid hydrolysis by amylase. Hydroxyethylstarch is removed from the circulation by renal excretion and by redistribution. Anaphylactoid reactions occur in about 0.09% of cases. Some patients experience severe pruritis. A particular concern is the possibility that starch preparations can affect the coagulation process. This issue has not been resolved but it seems prudent to avoid its use in patients with a coagulopathy. The maximum recommended dose is 20 mls/kg so its use in major resuscitation is limited