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
small but significance
incidence of adverse reactions (esp anaphylactoid reactions)
7.3.1 Molecular Weight
Two molecular weights are quoted for colloid
: Weight average molecular weight
: Number average molecular weight
(see Huskisson 1992 for definitions)
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
7.3 The Properties of an Ideal Colloid
to intravascular compartment only
special storage or infusion requirements
special limitations on volume that can be infused
interference with blood grouping or cross-matching
to all patients & no religious objections to its
easy to detect
should be 6 to 12 hours
be metabolised or excreted & not stored in the
& No Adverse Affect on Body Systems
interference with organ function even with repeated
non-allergenic & non-antigenic
interference with haemostasis or coagulation
cause agglutination or damage blood cells
affect on immune function including resistance to
affect on haemopoiesis
cause acid-base disorders
cause or promote infection (bacterial, viral or
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
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)
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
Polygeline is supplied as a 3.5% solution of ‘degraded
gelatin polypeptides cross-linked via urea bridges’ with
145, K+ 5.1, Ca++ 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 30C.
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%.
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.
• 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
• Favourable storage
characteristics: long shelf life, no refrigeration
• No interference with blood
• Compatible with other IV
fluids except Ca++
can cause problems with citrated blood products.
• Higher cost then
• Anaphylactoid reactions
• No coagulation factors and
its use contributes to dilutional coagulopathy
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.