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Colloids

Created: 20/4/2004
Updated: 14/5/2012

 

The colloids include:
Albumin
Dextran
Gelatins
Starches
Colloids also contain water and electrolytes, some are isotonic and others hyertonic, but they also contain a colloid, a large molecule that does not diffuse across semipermeable membranes.  The colloid therefore exerts an osmotic pressure in the blood, causing fluid to remain within the vascular system.  The result is an increase in intravascular volume.  These colloidal molecules can also take several hours to breakdown, therefore they have a longer lasting effect on intravascular volume than crystalloids, however benefits in efficacy are still being debated5. 
It would be a mistake to think that all colloids were the same, indeed they are not.  There are physicochemical differences, along with differences to the pharmacokinetics and safety profiles6. Two categories of colloid may be defined:
Natural e.g. human albumin
Artificial e.g. gelatins, dextran and hydroxyethyl starches (HES).
Their behaviour is determined by several factors.  These include:
Molecular weight – which determines the viscosity of the colloid
Molecular number – which influences the oncotic pressure
Osmolarity  - the measure of solute concentration, of which almost all colloids have a normal osmolarity6
Oncotic pressure – the higher the oncotic pressure the greater the initial volume expansion6
Plasma half-life – this will depend on the colloids molecular weight, route of elimination and the function of the involved organ
Plasma volume expansion – this is again dependant on the molecular weight.  On comparing the level of expansion between colloids and crystalloids, colloids  do exert greater plasma expansion for the same volume of fluid inserted
The acid –base  - some solutions have a physiological pH, whilst others tend to be acidic6
Natural colloids have the advantage of being associated with fewer side effects and greater volume expansion, however they are generally more expensive, and have been linked with causing increased leakiness of the vascular endothelium6 and possibly increasing interstitial oedema7. 
Synthetic colloids include Dextran, gelatins and starches.  Dextran, a highly branched polysaccharide has the advantage of being a volume expander whilst improving microcirculatory flow, however it also has the disadvantages of causing more severe anaphylactic reactions than other synthetic colloids, coagulation abnormalities i.e. decreased platelet adhesiveness, and it interferes with the ability to cross-match blood6. 
The colloids include:
Albumin
Dextran
Gelatins
Starches
Colloids also contain water and electrolytes, some are isotonic and others hyertonic, but they also contain a colloid, a large molecule that does not diffuse across semipermeable membranes.  The colloid therefore exerts an osmotic pressure in the blood, causing fluid to remain within the vascular system.  The result is an increase in intravascular volume.  These colloidal molecules can also take several hours to breakdown, therefore they have a longer lasting effect on intravascular volume than crystalloids, however benefits in efficacy are still being debated5. 
It would be a mistake to think that all colloids were the same, indeed they are not.  There are physicochemical differences, along with differences to the pharmacokinetics and safety profiles6. Two categories of colloid may be defined:
Natural e.g. human albumin
Artificial e.g. gelatins, dextran and hydroxyethyl starches (HES).
Their behaviour is determined by several factors.  These include:
Molecular weight – which determines the viscosity of the colloid
Molecular number – which influences the oncotic pressure
Osmolarity  - the measure of solute concentration, of which almost all colloids have a normal osmolarity6
Oncotic pressure – the higher the oncotic pressure the greater the initial volume expansion6
Plasma half-life – this will depend on the colloids molecular weight, route of elimination and the function of the involved organ
Plasma volume expansion – this is again dependant on the molecular weight.  On comparing the level of expansion between colloids and crystalloids, colloids  do exert greater plasma expansion for the same volume of fluid inserted
The acid –base  - some solutions have a physiological pH, whilst others tend to be acidic6
Natural colloids have the advantage of being associated with fewer side effects and greater volume expansion, however they are generally more expensive, and have been linked with causing increased leakiness of the vascular endothelium6 and possibly increasing interstitial oedema7. 
Synthetic colloids include Dextran, gelatins and starches.  Dextran, a highly branched polysaccharide has the advantage of being a volume expander whilst improving microcirculatory flow, however it also has the disadvantages of causing more severe anaphylactic reactions than other synthetic colloids, coagulation abnormalities i.e. decreased platelet adhesiveness, and it interferes with the ability to cross-match blood6. 
The colloids include:
Albumin
Dextran
Gelatins
Starches
Colloids also contain water and electrolytes, some are isotonic and others hyertonic, but they also contain a colloid, a large molecule that does not diffuse across semipermeable membranes.  The colloid therefore exerts an osmotic pressure in the blood, causing fluid to remain within the vascular system.  The result is an increase in intravascular volume.  These colloidal molecules can also take several hours to breakdown, therefore they have a longer lasting effect on intravascular volume than crystalloids, however benefits in efficacy are still being debated5. 
It would be a mistake to think that all colloids were the same, indeed they are not.  There are physicochemical differences, along with differences to the pharmacokinetics and safety profiles6. Two categories of colloid may be defined:
Natural e.g. human albumin
Artificial e.g. gelatins, dextran and hydroxyethyl starches (HES).
Their behaviour is determined by several factors.  These include:
Molecular weight – which determines the viscosity of the colloid
Molecular number – which influences the oncotic pressure
Osmolarity  - the measure of solute concentration, of which almost all colloids have a normal osmolarity6
Oncotic pressure – the higher the oncotic pressure the greater the initial volume expansion6
Plasma half-life – this will depend on the colloids molecular weight, route of elimination and the function of the involved organ
Plasma volume expansion – this is again dependant on the molecular weight.  On comparing the level of expansion between colloids and crystalloids, colloids  do exert greater plasma expansion for the same volume of fluid inserted
The acid –base  - some solutions have a physiological pH, whilst others tend to be acidic6
Natural colloids have the advantage of being associated with fewer side effects and greater volume expansion, however they are generally more expensive, and have been linked with causing increased leakiness of the vascular endothelium6 and possibly increasing interstitial oedema7. 
Synthetic colloids include Dextran, gelatins and starches.  Dextran, a highly branched polysaccharide has the advantage of being a volume expander whilst improving microcirculatory flow, however it also has the disadvantages of causing more severe anaphylactic reactions than other synthetic colloids, coagulation abnormalities i.e. decreased platelet adhesiveness, and it interferes with the ability to cross-match blood6. 
The colloids include:
Albumin
Dextran
Gelatins
Starches
Colloids also contain water and electrolytes, some are isotonic and others hyertonic, but they also contain a colloid, a large molecule that does not diffuse across semipermeable membranes.  The colloid therefore exerts an osmotic pressure in the blood, causing fluid to remain within the vascular system.  The result is an increase in intravascular volume.  These colloidal molecules can also take several hours to breakdown, therefore they have a longer lasting effect on intravascular volume than crystalloids, however benefits in efficacy are still being debated5. 
It would be a mistake to think that all colloids were the same, indeed they are not.  There are physicochemical differences, along with differences to the pharmacokinetics and safety profiles6. Two categories of colloid may be defined:
Natural e.g. human albumin
Artificial e.g. gelatins, dextran and hydroxyethyl starches (HES).
Their behaviour is determined by several factors.  These include:
Molecular weight – which determines the viscosity of the colloid
Molecular number – which influences the oncotic pressure
Osmolarity  - the measure of solute concentration, of which almost all colloids have a normal osmolarity6
Oncotic pressure – the higher the oncotic pressure the greater the initial volume expansion6
Plasma half-life – this will depend on the colloids molecular weight, route of elimination and the function of the involved organ
Plasma volume expansion – this is again dependant on the molecular weight.  On comparing the level of expansion between colloids and crystalloids, colloids  do exert greater plasma expansion for the same volume of fluid inserted
The acid –base  - some solutions have a physiological pH, whilst others tend to be acidic6
Natural colloids have the advantage of being associated with fewer side effects and greater volume expansion, however they are generally more expensive, and have been linked with causing increased leakiness of the vascular endothelium6 and possibly increasing interstitial oedema7. 
Synthetic colloids include Dextran, gelatins and starches.  Dextran, a highly branched polysaccharide has the advantage of being a volume expander whilst improving microcirculatory flow, however it also has the disadvantages of causing more severe anaphylactic reactions than other synthetic colloids, coagulation abnormalities i.e. decreased platelet adhesiveness, and it interferes with the ability to cross-match blood6. 

The colloids include:

  • Albumin
  • Dextran
  • Gelatins
  • Starches

Colloids also contain water and electrolytes; some are isotonic and others hypertonic, but they also contain a colloid, which is a large molecule that does not diffuse across semipermeable membranes. The colloid therefore exerts an osmotic pressure in the blood, causing fluid to remain within the vascular system. The result is an increase in intravascular volume. These colloidal molecules can also take several hours to break down; therefore, they have a longer lasting effect on intravascular volume than crystalloids, although benefits in efficacy are still being debated.

Differences in colloids


There are physicochemical differences, along with differences to the pharmacokinetics and safety profiles. Two categories of colloid may be defined:

  • Natural (e.g. human albumin)
  • Artificial (e.g. gelatins, dextran and hydroxyethyl starches [HES]).

Their behaviour is determined by several factors.  These include:

  • Molecular weight – which determines the viscosity of the colloid
  • Molecular number – which influences the oncotic pressure
  • Osmolarity - the measure of solute concentration, of which almost all colloids have a normal osmolarity
  • Oncotic pressure – the higher the oncotic pressure, the greater the initial volume expansion
  • Plasma half-life – this will depend on the colloid's molecular weight, route of elimination and the function of the involved organ
  • Plasma volume expansion – this is again dependent on the molecular weight.  On comparing the level of expansion between colloids and crystalloids, colloids exert greater plasma expansion for the same volume of fluid inserted
  • The acid–base balance - some solutions have a physiological pH, whil others tend to be acidic.

Natural colloids have the advantage of being associated with fewer side effects and greater volume expansion; however, they are generally more expensive and have been linked with causing increased leakiness of the vascular endothelium and possibly increasing interstitial oedema.

Synthetic colloids include dextran, gelatins and starches.  Dextran, a highly branched polysaccharide, has the advantage of being a volume expander while improving microcirculatory flow; however, it also has the disadvantages of causing more severe anaphylactic reactions than other synthetic colloids, coagulation abnormalities (i.e. decreased platelet adhesiveness), and it interferes with the ability to cross-match blood. 

Starling’s forces

(Ernest H Starling 1866-1927,  Physiologist, London, UK)

Most of an administered colloid remains intravascular unless an altered permeability condition is present. 


Transcapillary fluid balance: Starling's hypothesis

Starling's forces describe the factors determining the movement of fluid across the capillary endothelium. Movement into the interstitial space is driven by the hydrostatic pressure gradient. This flow is counteracted by the colloid osmotic gradient.

Net filtration= (Pc – Pif) – (¶p - ¶if  )

Pc = Capillary hydrostatic pressure (35 mmHg)

Pif = Interstitial hydrostatic pressure (usually zero)

¶p = Oncotic pressure due to plasma proteins (28 mmHg)

¶if  = Oncotic pressure due to interstitial proteins (3 mmHg)

Hence net flow:

Arterial end: 10 mmHg out of capillary       

Venous end: 10 mmHg into capillary

Albumin

• Natural protein
• Half-life (t½) = 20 days in the body, but t½ = 1.6 hours in plasma
• 10% leaves the vascular space within 2 hours, 95% within 2 days
• Causes 80-90% of our natural oncotic pressure
• Molecular weight (MW) 6.9 x 10-4
• Stays within the intravascular space unless the capillary permeability is abnormal
• 5% solution - isooncotic; 10% and 25% solutions - hyperoncotic
• Expands volume 5x its own volume in 30 minutes
• Effect lasts about 24-48 hours
• Side effects - volume overload, fever (pyrogens in albumin), defects of haemostasis

Overall, albumin may exert some mild effects on haemostasis; however, these effects seem to be primarily dilutional as a result of volume expansion. When large volumes of albumin are infused, the degree of volume expansion exceeds that obtained with a comparable amount of crystalloid solutions. Therefore, a more pronounced coagulation defect is likely.

Dextran

• High MW polysaccharide produced by Leuconostoc mesenteroides 
• Dextran 40 - MW 40,000 (greater effects on coagulation than D70) 
• Dextran 70 - MW 70,000 
• 10% solution in NS or D5W 
• Excretion is through the urine, faeces and reticulo-endothelial system (RES) (according to molecular size) 
• Side effects: anaphylaxis, coagulopathy, renal failure 
• Dose: limit to 20 ml/kg/day 
• Used for volume expansion 
• Used as antiaggregant in patients undergoing vascular and microvascular surgical procedures 

Clotting deficits associated with dextran are probably related to defects in platelet interaction and an antifibrinolytic effects. The platelet-vascular interaction is believed to be primarily associated with an effect on factor VIII. Dextran also seems to be incorporated into the polymerising fibrin clot so that it alters clot structure and enhances fibrinogenolysis. 

Dextran 40 is used in vascular surgery to prevent thrombosis but is rarely employed as a primary volume expander, alone or in combination with hypertonic saline. 

Gelatin

There are three types of gelatin solution currently in use in the world:

• Succinylated or modified fluid gelatins (e.g. Isoplex, Gelofusine) 
• Urea-cross-linked gelatins (e.g. Polygeline) 
• Oxypolygelatins (e.g. Gelifundol)

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-cross-linked using hexamethyl di-isocyanate. The branching of the molecules lowers the gel melting point. The MW ranges from 5000 to 50,000, with a weight-average MW of 35,000 and a number-average MW of 24,500.

• Rapidly excreted by the kidney
• t½ 2.5 hours
• Distribution (as a percentage of total dose administered) by 24 hours is 71% in the urine, 16% extravascular and 13% in the plasma. The amount metabolised is low, at ~3%
• Lower infusion volume required as compared with crystalloids
• Cheaper and more readily available than 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 20 ml/kg limit)
• Rapidly excreted by the kidney
• Long shelf life, no refrigeration
• No interference with blood cross-matching
• Compatible with other IV fluids, although Ca2+ can cause problems with citrated blood products

Dextran 

• High MW polysaccharide produced by Leuconostoc mesenteroides 
• Dextran 40 - MW 40,000 (greater effects on coagulation than D70) 
• Dextran 70 - MW 70,000 
• 10% solution in NS or D5W 
• Excretion is through the urine, faeces and RES (according to molecular size) 
• Side-effects: anaphylaxis, coagulopathy, renal failure 
• Dose: limit to 20 ml/kg/day 
• Used for volume expansion 
• Used as antiaggregant in patients undergoing vascular and microvascular surgical procedures 

Clotting deficits associated with dextran are probably related to defects in platelet interaction and an antifibrinolytic effects. The platelet-vascular interaction is believed to be primarily associated with an effect on factor VIII. Dextran also seems to be incorporated into the polymerising fibrin clot so that it alters clot structure and enhances fibrinogenolysis. 
Dextran 40 is used in vascular surgery to prevent thrombosis but is rarely employed as a primary volume expander, alone or in combination with hypertonic saline. 
Hetastarch (HES= hydroxyethyl starch)

• Synthetic hydroxy-substituted amylopectin, a highly branched glucose polymer
• MW= 10-4 to 10-5 variable weight
• 6% and 10% solution in normal saline solution
• Excreted in the urine (smaller particles), metabolised by blood amylase, then excreted into the bile and faeces (medium-sized molecules), or undergoes phagocytosis by the RES (larger molecules)
• May increase amylase levels from the salivary glands
• Plasma t½ is 5 days
• 90% eliminated in 40 days
• Remarkably free of toxicity
• Side effects: coagulopathy (coated platelets, increased fibrinolysis, decreased factor VIII level) but usually not a major clinical problem
• Dose: limit the amount to 20 ml/kg/d. However, amounts in excess of 15 litres have been used without significant coagulation problems.

Its effects have been studied in two major groups of patients. The first consists of healthy patients undergoing leukopheresis for donation of white blood cells. These patients usually receive small amounts (approximately 500 ml) of HES. In one study, 10 donors who received HES during leukopheresis had slight but significant prolongation of their prothrombin time and prolonged thromboplastin time (mean increases of 0.6 and 2.5 seconds, respectively). Levels of fibrinogen, factor VIII:C, and factor V were similarly reduced but remained within the normal range. In another report, no defects in platelet function were noticed. The second includes those who receive larger doses of HES for trauma and surgery. In these patients, a prolonged partial thromboplastin time and up to a 50% decrease in factor VIII:C occurs with an infusion of 1 L of HES.

In addition to its effect on levels of factor VIII:C, HES seems to cause changes in fibrin clot formation and fibrinogenolysis. This characteristic may be related to the incorporation of the HES molecules into the clot, with subsequent prevention of solid clot formation.

Pentastarch

Lower MW analogue of hetastarch; fewer OH-substitutions
• MW 250-350,000 kdaltons
• 10% solution in 500 ml normal saline solution vials
• 90% is cleared within 24 hours from administration
• Better volume expender than etastarch and albumin
• Approved by the FDA for plasmapheresis
• Available for volume expansion only in Europe
• Anticoagulation effects of pentastarch similar in type/magnitude to those of HES 

References

5. An Update on Intravenous Fluids by Gregory S. Martin, MD, MSc.

[
6. Mitra S et al.  Ind J Anaesth 2009; 53 (5):592-607.
i] Martin GS. An update on intravenous fluids.

[ii] Mitra S and Khandelwal P.  Indian J Anaesth 2009; 53: 592-607.

[iii] Park G.  Molecular mechanisms of drug metabolism in the critically ill. Br J Anaesth 1996; 77: 32-49.
7. Park G.  Br J Anaesth 1996; 77:32-49.


Related examination questions

1. Final SAQ: What fluids are available for the restoration of circulating volume in a patient suffering from acute blood loss? Discuss the advantages and disadvantages of each.

2. The ratio of intravascular hydrostatic pressure to colloid hydrostatic pressure (according to Starling’s forces) is greater:

a) in splanchnic capillaries than in renal glomerular capillaries
b) than normal in hepatic failure
c) than normal in haemorrhagic shock
d) than normal in capillaries where the oedema is due to venous obstruction
e) in systemic than in pulmonary capillaries

FTFTT


ArticleDate:20040420
SiteSection: Article
 
   
    
                                            
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