Colloid

Large MW (MW>30,000) substances

Problem

Higher cost

Small risk of anaphylactoid reaction

Mw: weight average MW
* Determines viscosity

Mn: number average MW
* Determines oncotic pressure

Albumin is monodisperse because all molecules have the same MW
* i.e. Mw = Mn

For artificial ones, polydisperse

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)

 

Dextrans

Highly branched poysaccharide molecules

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]

Dextran 70 has a duration of action of 6 to 8 hours

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

Disadvantage

• More severe anaphylactic reactions than the gelatins or the starches
  --> 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)
• Interference with crossmatching
  --> Need to notify lab
• Interference with haemostasis
  --> Induces an acquired von Willebrand’s state
  --> Maximal dosage recommendation of 20 mls/kg (about 1,500 mls in an adult)

 

Gelatins

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) 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, 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

Rapidly excreted by the kidney

Halflife 2.5hours

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 Ca++ 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

 

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Dextrose 5%

Maintenance Fluid (Dextrose is d-glucose)

Isosmotic as administered and does not cause haemolysis

Rapidly taken up by cells

The net effect is of administering pure water, so it is distributed throughout the total body water. Each compartment receives fluid in proportion to its contribution to the TBW (ie 2/3rd to ICF and 1/3rd to ECF; the ECF fluid is distributed one quarte to plasma & three quarters to ISF)

The distribution of 1,000 mls of dextrose 5% is:

• ICF 670mls
• ECF 330mls (with ISF 250mls and plasma 80mls)

Intravascular volume increases from 5000 to 5080 mls. This volume increase of less then 2% which will not be sensed by the volume receptors (as it is below the 7-10% threshold)

The osmolality of plasma (3,200 mls) will decrease by: [ 287 - (287 x 3.20 / 3.28) ] which is about 7 mOsmoles/l or a 2.5% decrease. This is enough to be detected by the osmoreceptors. ADH release will be decreased and renal water excretion will rise. A delay will occur because the changes have to be detected centrally and then ADH levels need 3 half-lifes to fall to a new steady state

 

Normal Saline

ECF Replacement Fluid

Its [Na+] is similar to that of the extracellular fluid and this effectively limits its distribution to the ECF (distributing between the ISF & the plasma in proportion to their volume ie 3:1)

The ISF will increase in volume by 750 mls. The plasma volume will increase by 250 mls. This is why blood loss of 1,000 mls requires about 3 to 4 times the volume of IV replacement fluid to restore normal intravascular volume

Plasma osmolality and tonicity will be unchanged because normal saline is isosmotic. The osmoreceptors do not contribute anything to the excretion of normal saline. Blood volume increases to 5250 mls; an increase of 5%. This is below the sensitivity of the volume receptors. It seems that the body has no clear way of excreting this excess fluid as neither osmoreceptors nor volume receptors are stimulated!

However, experiments have shown that replacement fluids are excreted the most rapidly of all these groups!

How does this happen? An additional mechanism is relevant here. Normal saline contains no protein so the oncotic pressure in the blood is slightly lowered following the saline infusion. This has 2 effects:

Movement of fluid into the ISF is favoured (Starling’s Hypothesis)

Glomerulo-tubular imbalance occurs: the lowered oncotic pressure immediately leads to an increase in GFR and a smaller reabsorption of water in the proximal tubule. Urine flow increases. This is a strictly local effect without any hormonal intermediary. The urine flow increases immediately. Fluid then moves back into the intravascular compartment and the urine flow continues until all the transfused fluid is excreted.

Plasma Protein Solution

Plasma protein solution is a colloid and is distributed only to the intravascular fluid. The tonicity is unaltered. The blood volume increases from 5,000 mls to 6,000 mls; an increase of 20%. This is above the 7 to 10% threshold for the volume receptors. The result is a fall in ADH levels and the excretion of the excess water commences.

This water loss tends to increase the plasma oncotic pressure and water moves from the ISF to the IVF. Vascular reflexes are important also in causing venous pooling and a decrease in the ‘effective’ circulating volume. These mechanisms tend to slow the excretion of the water load. The albumin is partly slowly redistributed to the ISF and metabolised. These changes are slow so the effect of plasma protein infusion on blood volume is both more pronounced and more prolonged.

The pressure-volume control mechanisms important in long term regulation of blood volume are slow in onset but become relevant here as the blood volume change is more significant and more prolonged and occurs without change in osmolality (or initially in plasma oncotic pressure either).

Overview

Dextrose 5% is essentially treated by the body as pure water and a significant percent moves intracellularly. It is a useful fluid to replenish intracellular fluid but does so at the expense of tonicity. It is inappropriate for intravascular volume replacement. It is excreted because ADH levels decline in response to the drop in plasma osmolality.

Normal saline is a replacement fluid (meaning ECF replacement) because it adds only to the ECF volume. Only about a third remains intravascularly. To replace intravascular volume will require transfusion with about 3 times the volume of blood lost. It is cheap and readily available. It is excreted because the small drop in plasma oncotic pressure causes glomerulotubular imbalance. ADH is not affected.

Plasma protein solutions (eg 5% human albumin) are excellent for replacing intravascular volume. ISF and ICF will not be replenished. Albumin is slow to be excreted and the transfused volume is excreted much slower than with replacement solutions. Plasma protein solutions are expensive and supply is limited. The fluid is initially excreted because of a fall in ADH level falling stimulation of the volume receptors.

 

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Effects of Mannitol
Osmotic Effects (due hypertonicity)
    * Intracellular dehydration
    * Expansion of ECF volume (except brain ECF)
    * Haemodilution
    * Diuresis due osmotic effects and ECF expansion
Non-Osmotic Effects
    * Decreased blood viscosity (with improved tissue blood flow)
    * Possible Cytoprotective effect (due free radical scavenging)
    * Cardiovascular effects secondary to expanded intravascular volume (eg increased cardiac output, hypertension, heart failure, pulmonary oedema)