Colloids - an overview
Dr. S. Parthasarathy
MD., DA., DNB, MD (Acu),
Dip. Diab. DCA, Dip. Software statistics
PhD (physio)
Mahatma Gandhi medical college and
research institute , puducherry – India
Colloids
• Colloids tend to be larger molecules than
crystalloids
• dispersed throughout the solvent rather than
forming true solutions.
• The component particles tend to arrange as
groups of molecules and so do not readily pass
through clinical semipermeable membranes.
• They therefore have an oncotic potential that is
usually measured as colloid osmotic pressure
(COP).
Image of a colloid
But crystalloids !!!
• Crystalloid solutions are solutions of sugar or
salt or mixture of salt and sugar in water.
• Crystalloids remain intravascular for short
period and metabolise to carbon dioxide,
water, ions and yields energy.
In simple terms
• Osmotic pressure
• Exerted by salts to push fluid out
• Oncotic pressure exerted by colloids to get
fluid in the blood vessel
Colloids
• Colloids are solutions of high molecular
weight substances that largely remain in the
intravascular compartment for longer period
and generate an oncotic pressure as well as
slowly being metabolized.
Colloids
• number of molecules per volume of solution is
usually lower than crystalloid solution.
• No effect on osmolarity
• Hence electrolytes are added.
Half life
• the intravascular half-life of a crystalloid
solution is 20–30 min,
• most colloid solutions have intravascular halflives between 3 and 6 h.
Characters
• General characteristics of the colloid are
• (i) particles have high molecular weight,
• (ii) high osmolality. and high oncotic pressure
(iii) longer plasma half life
• (iv) higher plasma volume expansion
• 25 % Vs 125%
Types of colloids
• colloids are either natural or artificial.
• The natural colloids are blood, human
albumin and fresh frozen plasma.
• Artificial colloids are dextrans, gelatins and
starch. Artificial colloids are polymers
containing molecules with wide range of
molecular weight
• Monodisperse and polydisperse
Characters
• Molecular weight : oncotic pressure
• Osmolality and oncotic pressure: Almost all
colloid solutions have a normal osmolality.
The oncocity of the solution will influence the
vascular expansion.
• Plasma half-life: The plasma half-life of a
colloid depends on its MW, the elimination
route, and, the involved organ function
(mainly eliminated by the renal route
Characters
• MW --- oncotic pressure – initial volume
expansion ---- half life – persistence
• The degree of volume expansion is mainly
determined by the MW, whereas the
intravascular persistence is also determined by
the elimination of the colloid.
Characters
• Acid-base composition: Albumin and gelatin
solutions have physiological pH, while other
solutions tend to have acidic pH.
• Electrolyte content: The sodium
concentration is low in “salt-poor albumin
Others same
Human albumin solution
• principal natural colloid comprising 50 to 60%
of all plasma proteins
• contributes to 80% of the normal oncotic
pressure in health.
• MW = 69,000 Dalton
• Synthesis – liver
Human albumin solution
• 5% solution is isooncotic and leads to 80%
initial volume expansion
• 25% solution is hyperoncotic and leads to 200
- 400% increase in volume within 30 minutes.
• The effect persists for 16 - 24 h
Structure of albumin
Indications:
• a. Emergency treatment of shock specially due to
the loss of plasma
• b. Acute management of burns
• c. Fluid resuscitation in intensive care
• d. Clinical situations of hypo-albumineamia
i. Following paracentesis
ii. Patients with liver cirrhosis (For
extracorporeal albumin dialysis (ECAD))
iii. After liver transplantation
• e. Spontaneous bacterial peritonitis
• f. Acute lung injury
Advantages:
•
•
•
•
•
Natural
Volume expansion
possesses antioxidant and scavenging effects
Disadvantages:
Costly , ‘leakiness’ of the vascular
endothelium and volume overload
Dextran
• highly branched polysaccharide molecules
• Artificial
• synthesis using the bacterial enzyme dextran
sucrase from the bacterium Leuconostoc
mesenteroides
• 6% solution with an average molecular weight
of 70,000 (dextran 70)
• 10% solution with an average weight of
40,000 (dextran 40, low-molecular-weight
dextran)
characters
• Kidneys primarily excrete dextran solutions.
• Both dextran-40 and dextran-70 lead to a
higher volume expansion as compared to HES
and 5% albumin. (100 to 150%)
• The duration lasts for 6–12 hours
Dextran – slowly decreasing uses
• used mainly to improve micro-circulatory flow
in microsurgical re-implantations.
• Extracorporeal circulation:
Disadvantages
• Anaphylactic reactions:
• Coagulation abnormalities:
• Interference with cross-match:
• Precipitation of acute renal failure:
Gelatins
• Gelatin is the name given to the proteins
formed when the connective tissues of
animals are boiled
• If you cool, it may gellify !!
Modified gelatins
• Succinylated or modified fluid gelatins (e.g.,
Gelofusine, Plasmagel, Plasmion)
• Urea-crosslinked gelatins (e.g., Polygeline)
• Oxypolygelatins (e.g., Gelifundol)
• Polygeline (‘Haemaccel’, Hoechst) is produced
by the action of alkali and then boiling water
(thermal degradation) on collagen from cattle
bones.
• MW = 35000
haemaccel
• . Polygeline is supplied as a 3.5% solution with
electrolytes (Na+ 145, K+ 5.1, Ca++ 6.25 & Cl −
145 mmol/l).
• calcium ions -- increase in serum calcium
concentration following large volume
resuscitation.
• Polygeline also contains potassium ions:
Succinated gelatin
Character and indications
•
•
•
•
•
•
Kidneys excrete
70 -80 % volume expansion
2 -3 hours
Hypovolemia due to acute blood loss.
Acute normovolaemic haemodilution.
Extracorporeal circulation – cardiopulmonary bypass.
• Volume pre-loading prior to regional anaesthesia.
•
ADVANTAGES AND DISADVANTAGES
• Cost effective:
• No limit of infusion:
• No effect of renal impairment:
• Higher anaphylaxis than albumin
• Coagulation – platelet adhesions decreased
• Increased PRA and possible circulatory
problems
Hydroxyethyl starches (HES)
• Starch is polysaccharide carbohydrate and
seen to produce less morbidity compared to
dextrans or gelatins.
• As a class, starch is safer than other colloid
and is a near – ideal resuscitation fluid.
How to get
amylopectin rich corn
• Amylases
glucose molecules
• Hydroxy ethylation
• neutralised with alkali and further purified
• HES
Voluven
HES
• Concentration: low (6%) or high (10%).
• Molecular Weight (MW): low ( 70 kDa), medium
( 200 kDa), or high ( 450 kDa).
•
•
•
•
Polydisperse
Small excreted
Large fragmented to small
continuous supply of oncotically active molecules
• Molar substitution (MS): low (0.45–0.58) or
high (0.62–0.70)
• A varying number of hydroxyethyl residues
attached to the anhydrous glucose particles
within the polymer.
• increases the solubility of the starch in water,
inhibits the rate of destruction of the starch
polymer by amylase.
MS !! What is this ??
• The figure 0.7 in the description of a HES
preparation indicates that there are seven
hydroxyethyl residues on average per 10
glucose subunits.(hetastarches)
• hexastarch (MS 0.6),
• pentastarch (MS 0.5),
• tetrastarch (MS 0.4).
• C2/C6 ratio: low (<8) or high (>8).
• The C2/C6 ratio refers to the site where
substitution has occurred on the initial
glucose molecule.
• The higher the C2/C6 ratio, longer the half-life
and hence, longer persistence in the blood
Metabolism
• initially a rapid amylase-dependent breakdown and
renal excretion.
• Plasma half life is 5 days and 90% is eliminated in 42
days.
• Smaller HES molecules (<50,000 to 60,000 Dalton) are
eliminated rapidly by glomerular filtration.
• Medium sized molecules get excreted into the bile and
faeces.
• Another fraction - taken up by the reticuloendothelial
system where the starch is slowly broken down.
Detected for several weeks after administration
Advantages
• Volume expansion 100%
• Duration 8-12 hours
•
•
•
•
Shock
Endotoxemia
Maximal – 50 ml/kg
Cost less than albumin
Problems
•
•
•
•
Coagulation
Renal impairment
Accumulation and itching
Anaphylactoid reactions
• But ? Found in third generation – tetrastarch
!!
pharmacokinetics
• Clearance of the latest generation (third
generation) 130/0.4) is 20 to 30 fold higher
compared to first generation HES
• therapeutic safety index of third generation
HES (130/0.4) (C2-C6 >8) is higher compared
with all other HES solutions
Third-generation HES: tetrastarch
v
• Reductions in MW and MS have led to
products with shorter half-lives,
• improved pharmacokinetic
• pharmacodynamic properties,
• fewer side effects
Benefits over older starches
• reduced effect on the coagulation process
compared to older products
• rapid clearance of the latest generation of
tetrastarches, - less accumulation
• Less tissue persistence – less itching
Benefits over older starches (130/0.4)
• Waxy maize better over potato derived in liver
dysfunction
• Renal dysfunction, elderly, hepatic dysfunction
,Cardiac surgery, abdominal aortic surgery
• Also children
Effects on Microcirculation and
Oxygenation
• beneficial
effects
microcirculation,
on
organ
tissue
perfusion,
oxygenation,
inflammation, endothelial activation, capillary
leakage, and tissue edema over and above
their volume replacement effects
• We are using them in shock states
Crystalloids Vs colloids
• Intravascular persistence
• Volume expansion
•
•
•
•
Anaphylaxis,
Renal
Cost
Coagulation
Trials
• 1989 – may be more deaths with colloids
• no difference in outcome among patients treated
with colloids or crystalloids (BMJ – 1998)
• SAFE (Saline versus Albumin Fluid Evaluation) trial
• 7000 critically ill patients requiring fluid
resuscitation to receive isooncotic albumin or
isotonic crystalloid.
• There was no overall difference in outcome
The danger starts
FDA recommendations – June 2013
• Do not use HES solutions in critically ill adult patients
including those with sepsis, and those admitted to the
ICU.
• Avoid use in patients with pre-existing renal
dysfunction.
• Discontinue use of HES at the first sign of renal injury.
• Need for renal replacement therapy has been reported
up to 90 days after HES administration.
• Avoid use in patients undergoing open heart surgery in
association with cardiopulmonary bypass due to excess
bleeding.
• Discontinue use of HES at the first sign of coagulopathy.
• This is an overview
• Read well for more details
• Are colloids – boon to gloom !!
Thank you all