This document provides an overview of colloids used for fluid resuscitation. It defines colloids and discusses their history, studies, scientists involved in research, and physiology. The document classifies and describes different types of colloids including albumin, dextran, and hydroxyethyl starches. It compares the differences between crystalloids and colloids, and concludes with a discussion of appropriate use and monitoring of colloid administration.

1. Presented by- Dr RICHIE SANAM
1ST YEAR PG
MODERATOR- Dr PRADEEP MD
Assistant PROFESSOR
Date: 6-8-16

2.  DEFINITION
 HISTORY
 STUDIES
 SCIENTISTS
 PHYSIOLOGY
 CLASSIFICATION
 DESCRIPTION
 DIFFERENCES BETWEEN CRYSTALLOIDS AND COLLOIDS
 CONCLUSION

3.  Colloid is defined as large molecules or ultramicroscopic
particles of a homogeneous non crystalline substance dispersed
in a second substance, typically isotonic saline, or a
balanced crystalloid .
 These particles cannot be separated out by filtration or
centrifugation.
 1ml blood loss-1ml colloid-3ml crystalloid.

4.  Fluid therapy with water and salts was probably first given in the 1830s for
treatment of patients suffering from Blue Cholera.
 Thomas Graham’s investigations on diffusion led him to classify substances
as crystalloids or colloids based on their ability to diffuse through a
parchment membrane.
 With crystalloids significant improvement in clinical symptoms occurred but
outcomes were poor, attributed in part to the lack of a sustained effect.
 Over the next 70 years the use of IV crystalloid solutions became more
widespread however the short term effects of crystalloids lead clinicians to
try and develop new solutions that would “remain in the circulation longer”.

5.  Gelatin, was the first fully artificial plasma substitute to be used
extensively for shock treatment in hypovolemic patients during first
world war.

 By the end of world war II use of colloid for resuscitation was well
established and dextrans as well as Gelatins were used as a substitute
to plasma for resuscitation.
 By 1985 it was being suggested that the end of routine use of
crystalloid solutions as volume expanders was approaching.
 over the following years a number of systematic reviews and meta-
analysis suggested that there may be adverse events and worse
outcomes associated with the use of synthetic and natural colloids.

8.  Cochrane collaboration in 1998 implicated that the use of human
albumin in excess mortality sparked immediate publicity and the call for
a ban on albumin use.
 New Zealand Intensive Care Society Clinical Trials Group(ANZICS-CTG)
proposed the SAFE study – a double blind evaluation of 4% albumin vs
saline for volume resuscitation in intensive care.
 the SAFE study represented the largest RCT performed in intensive
care patients and demonstrated that the use of albumin was safe (with
the exception of patients with TBI), however no clinical benefits could
be shown over saline.

9.  Colloid solutions are used as resuscitative fluids in severe shock
states.
 Two chemists received the Nobel Prize for their pioneering
work on these colloidal solutions.
 Richard Zsigmondy (April 1, 1865 – Sept23, 1929): Austrian
chemist who received the Nobel Prize for Chemistry in 1925 for
research on colloids.

10.  Theodor H. E. Svedberg (Aug 30, 1884 - Feb25, 1971): Swedish
chemist who won the Nobel Prize for Chemistry in 1926 for his
studies inthe chemistry of colloids and for his invention of the
ultracentrifuge, an invaluable aid in those and subsequent
studies.

11. Austria, 1979, 50th
Anniversary of Richard
Zsigmondy
Sweden 1983, Nobel Prize
winners for
Chemistry, stamp
depicting colloids
Yemen Arab Republic
1966, stamp
depicting
Zea Mays

12.  COLLOIDAL OSMOTIC PRESSURE
 THE MOVEMENT OF WATER INTO THE CCOMPARTMENT WITH THE HIGHER
SOLUTE CONCENTRATION CREATES AN INCREASE IN PRESSURE IN
COMPARTMENT AND THIS PRESSURE INCREMENT IS EQUAL TO OSMOTIC
PRESSURE.
 HENCE OSMOTIC PRESSURE CAN BE DEFINED AS
 “DRIVING FORCE FOR THE MOVEMENT OF WATER INTO FLUID COMPARTMENT”
 COLLOID OSMOTIC PRESSURE OF PLASMA-25mmHg.
 Proteins mostly albumin present in plasma create colloid osmotic pressure or oncotic
pressure.

13.  . Two categories of colloid may be defined
 Natural (e.g. human albumin)
 Artificial (e.g. gelatins, dextran and hydroxyethyl starches
[HES]).

14.  Colloids also contain water and electrolytes; some are isotonic
and others hypertonic, but they also contain a colloid.
 The colloid therefore exerts an osmotic pressure in the blood,
causing fluid to remain within the vascular system resulting in
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.

15.  There are physicochemical differences, along with differences
to the pharmacokinetics and safety profiles.
 Natural colloids have fewer side effects and greater volume
expansion; however more expensive causing increased leakiness
of the vascular endothelium and possibly increasing interstitial
oedema.

16.  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.

17.  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.

18. 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.

20.  Principal Natural colloid, Contributes to 80% of oncotic pressure
 single polypeptide chain of 585aminoacids
 Molecular weight (MW) - 69000daltons
 Albumin has a half life of 15-20 days in the circulation , with a turnover of
approximately 15 g per day.
 BINDING AND TRANSPORT OF LOW MOL WT SUBSTANCE LIKE
BILIRUBIN AND CERTAIN DRUGS
.

21.  Commercially available preparation is a heat treated preparation
of human serum albumin
 5% albumin solution-50g/l
 25% albumin solution-250g/l
 Plasma protein fraction

22.  Will expand circulating blood volume by an
amount approximately equal to the volume
infused
 5% solution is iso-oncotic and leads to 80%
initial volume expansion
 Colloidal osmotic pressure of 20 mmhg
 Also referred to as SALT POOR ALBUMIN
 Used in treatment of shock associated with
surgery ,haemorrhage, trauma ,burns,
renal failure and cardiovascular collapse

23.  NON PHYSIOLOGIC HYPERONCOTIC FLUID
 Contains 96% albumin and 4% globulin
 Colloid solution of 25%albumin contains purified albumin at 5
times the normal concentation
 COLLOIDAL OSMOTIC PRESSURE OF 70mmHg
 Potential to expand intravascular volume by 4-5 times the volume
provided
 THIS INCREASE IN FLUID SHIFT IS FROM INTERSTITIAL
FLUID,SO IT SHOULD NOT BE USED IN VOLUME
RESUSCITATION

24.  EMERGENCY TREATMENT OF HYPOVOLEMIC SHOCK
 BURN THERAPY
 ACUTE LIVER FAILURE
 CORRECTION OF HYPOPROTEINEMIA IN DIURETIC
RESISTANT NEPHROTIC SYNDROME AND MALNUTRITION
 AS A EXCHANGE FLUID FOR THERAPUETIC
PLASMAPHERESIS

25.  HYPERSENSITIVITY
 CIRCULATORY OVERLOAD IN PATIENTS WITH CCF, RENAL
FAILURE
 HYPOPROTEINEMIC STATES ASSOCIATED WITH CHRONIC
CIRRHOSIS, MALABSORPTION AND PANCREATIC
INSUFFICIENCY

26.  NAUSEA,VOMITING AND ALLERGIC REACTION INCLUDING
ANAPHYLACTIC SHOCK
 CIRCULATORY OVERLOAD
 FEBRILE REACTION
 HYPOTENSION-PPF INFUSED >10ML/MIN

27.  DON’T USE CLOUDY SOLUTIONS OR SOLUTIONS WITH DEPOSITS
 ALBUMIN SOLUTIONS SHOULD NOT BE DILUTED WITH WATER FOR INJECTIONS-
HEMOLYSIS
 RELATIVELY LOW IN ELECTROLYTES-ELECTROLYTE STATUS SHOULD BE
MONITORED
 SHOULD NOT BE USED FOR VOLUME RESUSCITATION IN HYPOVOLEMIC PATEINTS
UNLESS TREATED WITH CRYSTALLOIDS
 CARE MUST BE TAKEN TO ENSURE ADEQUATE SUBSTITUTION OF COAGULATION
FACTORS PLATELETS AND ERYTHROCYTES
 SHOULD NOT BE USED FOR PARENTERAL NUTRITION
 HYPERVOLEMIA MAY OCCUR WITH FAST INFUSION LEADING TO VASCULAR
OVERLOAD AND PULMONARY EDEMA

28.  BEING A NATURAL COLLOID ASSOCIATED WITH LESSER
SIDE EFFECTS LIKE PRURITUS ANAPHYLACTOID
REACTIONS AND COAGULATION ABN WHEN COMPARED TO
SYNTHETIC COLLOIDS
 GREATER DEGREE OF VOLUME EXPANSION-25% ALBUMIN
WHEN COMPARED TO REST OF COLLOIDS
 DISADVANTAGES
 COST EFFECTIVENESS
 VOLUME OVERLOAD

29.  ADJUSTED TO PATIENTS INDIVIDUAL REQUIREMENTS
 MEASURES OF ADEQUACY OF CIRCULATING VOLUME AND NOT PLASMA
ALBUMIN LEVELS
 HEMODYNAMIC PERFORMANCE TO BE MONITORED
 ARTERIAL BLOOD PRESSURE AND PULSE RATE
 CVP
 PAWP
 URINE OUTPUT
 ELECTROLYTES
 HEMOGLOBIN/HEMATOCRIT
 5%ALBUMIN-INFUSED AT A RATE OF1-2ml/min
 25%albumin-INFUSED AT A RATE OF 1ml/min

30.  High MW polysaccharide produced by Leuconostoc mesenteroides incubated in
SUCROSE MEDIUM
 AVAILABLE IN TWO FORMS
 Dextran 40 - MW 40,000 (greater effects on coagulation than D70) -
10%solution
 Dextran 70 - MW 70,000- GREATER EXPANSION BUT SHORTER
DURATION OF ACTION -6%solution
 COLLOIDAL OSMOTIC PRESSURE OF 40 mmHg
 Dextrans have a plasma volume effect similar to that of starches, with a
duration of 6 to 12 hours.

31.  Not a substitute for whole blood because it has no oxygen
carrying capacity
 Not a substitute for plasma proteins-lack of clotting factors
 Improvement of microcirculation and prevention of
thromboembolism
 cause a greater increase in plasma volume than either 5%
albumin or 6% hetastarch .
 Dextran-70 may be preferred because the duration of action
(12 hours) is longer than that of dextran-40 (6 hours)

32.  CORRECTION OH HYPOVOLEMIA
 PROPHYLAXIS OF DVT AND POST OPERATIVE AND POST
TRAUMATIC THROMBOEMBOLISM
 TO IMPROVE BLOOD FLOW AND MICROCIRCULATION IN
THREATENED VASCULAR GANGRENE

33.  A proportion of smaller MW molecules that are present are
rapidly filtered at the glomerulus.
 70% of a dextran dose is renally excreted within 24 hours.
 Higher MW molecules are excreted into the GI tract or taken
up into the mononuclear phagocyte system, where they are
degraded by endogenous dextranases

34.  Side effects:
 anaphylaxis,
 coagulopathy,
 renal failure
 Dose: limit to 20 ml/kg body wt in adults

35. Overall the use of dextrans are limited by their toxicity

36.  This is particularly marked in lower MW dextrans and is
mediated through a range of mechanisms, including
 red cell coating and inhibition of aggregation
 factor VIIIc and vWF reductions
 impaired activity of factor VIII.
 Platelet aggregation is also inhibited.
 The result is clinically impaired hemostasis and
increasedperioperative blood loss.

37.  Cross matching
 Anaphylactoid reactions
 Renal dysfunction

38.  HYPERSENSITIVITY
 MARKED CARDIAC DECOMPENSATION
 RENAL DISEASE WITH SEVERE OLIGURIA OR ANURIA
 MARKED HEMOSTATIC DEFECTS
 Example-thrombocytopenia hypofibrinogenimia

39.  Gelatins are derived from the hydrolysis of bovine collagen,
with subsequent modification by succinylation (Gelofusine,
B Braun, Bethlehem, Pa; Geloplasma,Fresenius, Waltham, Mass)
or
 urea-linkage to form polygeline (Haemaccel, Piramal
 , Orchard Park, NY).

40. 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.


41.  Synthetic colloid
 Degraded gelatin
 Concentration - 3.5%
 Half life – 2-3 hr
 Dose – 20 ml/kg/day
 Osmotic pressure – 300 mmHg

42.  Indications:
 Hemorrhagic Shock
 Post-spinal Hypotension
 Anaphylactic Shock
 Hemodiluent in acute normovolemic hemodilution
 Surgical Patients with MS/AS
 Contra-indications:
 Patients with Atopy
 Bronchial Asthma
 Septicemia
 Pulmonary edema/ARDS
 Hypertension
 Patients with unknown Blood Group
 Bleeding Diathesis

43.  Potential fatal histamine reactions
 Facial flushing to severe anaphylactic reactions
 Rarely air embolism when infused under pressure
 Treatment-
 Mild reactions – administer antihistamines
 Severe reactions- inject catecholamines plus high doses of
corticosteroids slow iv
 CONTRAINDICATIONS
 hypersensitivity
 Existing severe allergic reactions

44.  Derived from maize starch (amylopectin)
 Substitution of hydroxyethyl radicals onto glucose units
prevents rapid in vivo hydrolysis by amylase
 the degree of substitution both in terms of hydroxyethyl
substitutions per glucose unit (maximum three) and total number
of glucose units with substitutions is a determinant of HES
kinetics of elimination.

45.  The degree of substitution (DS) is expressed as the number of
substituted glucose molecules present divided by the total
number of glucose molecules present.
 An alternative measure of substitution is the molar substitution
(MS) ratio, calculated as the total number of hydroxyethyl
groups present divided by the quantity of glucose molecules.

46.  Classification of HES depends on molar substitution
 Hetastarch (0.7), e.g., Hespan, Hextend
 Pentastarch (0.5), e.g., Pentaspan
 Tetrastarch (0.4), e.g., Voluven
Product MW (k
D)
C2/C6 Ratio
(Ratio of CH2CH2OH
groups at C2 vs. C6)
Molar Substitution
(Number of CH2CH2OH g
roups per glucose subun
it)
Half-
Life (ho
urs)
Hespan/
Hextend
670 5:1 0.7 46.3
Voluven 130 9:1 0.4 12.1
HIGHER MS VALUES SLOWS HYDROLYSIS

47.  HYDROXYETHYLATION CAN OCCUR AT CARBON 2,3 AND 6
POSITIONS OF GLUCOSE UNIT
 C2/C6 ratio (number of hydroxyethyl (CH2CH2OH) groups at C2
vs. C6 of glucose subunits)
 HIGHER RATIO LEADS TO SLOWER STARCH METABOLISM

48.  Synthetic colloid
 6% and 10% solution in normal saline solution
 Composed of more than 90% esterified amylopectin
 Esterification leads to longer plasma volume expansion
 6%hetastarch which is normally used molecular weight of
4,50,000
.

49.  3types based on molecular weight
 High molecular weight
 Medium molecular weight
 Low molecular weight
 Excretion
 Low mol wt HES are readily excreted in urine in 24hrs
 Large mol wt HES are metabolised and eliminated slowly

50.  NON ANTIGENIC
 DOESN’T INTERFERE WITH BLOOD GROUPING
 LESS EXPENSIVE THAN ALBUMIN
 PLASMA VOLUME EXPANSION GREATER THAN 5% ALBUMIN
 EFFECTS LAST FOR ABOUT 24 HRS
 DISADVANTAGES
 MACROAMYLESEMIA
 NO OXYGEN CARRYING CAPACITY

51.  Remarkably free of toxicity
 Side effects: coagulopathy (coated platelets, increased
fibrinolysis, decreased factor VIII level) but usually not a major
clinical problem
 VOMITING FEVERISHNESS URTICARIA AND WHEEZING
 PRURITUS
 Dose: limit the amount to 20 ml/kg/d.

52.  SAFER AND EFFECTIVE PLASMA EXPANDER
 CORRECT HYPOVOLEMIC SHOCK
 CONTRAINDICATIONS
 BLEEDING DISORDER
 CONGESTIVE HEART FAILURE
 IMPAIRED RENAL FUNCTION

53.  Lower MW analogue of hetastarch; fewer OH-substitutions .
 Available as 3% ,6% and 10% solutions.
 Pentastrarch differs from heta starch in having a lower degree of esterification.
 Better volume expander than hetastarch and albumin .
Approved by the FDA for plasmapheresis.
Anticoagulation effects of pentastarch similar in type/magnitude to those of HES .
 10% pentastarch can increase plasma volume 1.5 times.

55. COLLOIDS CRYSTALLOIDS
LARGER INTRAVOLUME EXPANSION INEXPENSIVE
IMPROVES CARDIAC OUTPUT EASILY AVAILABLE
OPEN UP MICROCIRCULATION NON ALLERGENIC
DONOT CONTRIBUTE TO INTERSTITIAL EDEMA DON’T INTERFERE WITH COAGULATION
CAN BE RAPIDLY DIVERSED

56.  Greater Expense larger volumes needed
 Coagulopathy don’t carry oxygen
 (Dextran>HES)
 Interferes in contribute to peripheral and
 Grouping & Cross matching pulmonary edema
 Pulmonary Oedema redistribution within hour
 (Septicemia & ARDS)
 Decreased GFR
 Osmotic Diuresis
 Hypocalcemia
 (with Albumin)

57. No single resuscitation fluid will perform optimally in all conditions associated with
hypovolemia.
So it should PROBLEM BASED APPROACH
 1. In cases of life-threatening hypovolemia from blood loss (where a prompt
increase in plasma volume is necessary), an iso-oncotic colloid fluid (e.g., 5%
albumin) would be most effective.
 2. In cases of hypovolemia secondary to dehydration (where there is a uniform loss
of extracellular fluid), a crystalloid fluid (e.g., Ringer’s lactate) is appropriate.
 3. In cases of hypovolemia where hypoalbuminemia is implicated (causing fluid
shifts from plasma to interstitial fluid) a hyperoncotic colloid fluid (e.g., 25%
albumin) is an appropriate choice.

58. Type of fluid Effective plasma
expansion/100ml
Duration
5% albumin 70-130 ml 16hrs
25% albumin 400-500 ml 16hrs
6%hetastarch 100- 130ml 24hrs
10% pentastarch 150 ml 8hrs
10%dextran 40 100-150ml 6hrs
6% dextran 70 80 ml 12hrs

59.  SINCE THE GOAL OF RESUSCITATION IS TO SUPPORT THE
INTRAVASCILAR VOLUME COLLOID FLUIDS ARE LOGICAL
CHOICE OVER CRYSTALLOIDS.
 Sir Henry Tizard’s introductory quote to resuscitation fluids,
The secret to select the appropriate resuscitation fluid is to
ask the question
“what is the cause and severity of the hypovolemia in this
patient?”