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Colloid Solutions
To Use or not to Use?

Ubaidur Rahaman
Associate Consultant Critical Care Medicine
Fortis Flt. Lt. Rajan Dhall Hospital
New Delhi 110070
“the LV volume is a surrogate for LV wall tension
And the LV wall tension a surrogate for LV stroke volume

And the LV stroke volume determines CO
And the LV CO is a surrogate for tissue blood flow
And tissue blood flow is a surrogate for tissue oxygenation
And the tissue oxygenation is a surrogate for ATP generation
And ATP generation powers cellular function”
COLLOIDS

NATURAL
Albumin

SYNTHETIC
Gelatin
Starch
Dextran
STARCH
SYNTHETIC COLLOIDS

10% Pentaspan 250/0.45
6% Hespan 450/0.60
6% Voluven 130/0.40
Classification of Strarch
Concentration
Molecular weight
Degree of substitution
C2:C6 ratio
Concentration= Oncocity
Plasma- 25 mmHg
10% Pentaspan- 80 mmHg
6% Voluven- 26 mmHg
Molecular weight
HES are polydispersible substances.
They contain a distribution of molecular weights.
The number on the package is the average
Molecular weight
After infusion the molecules are broken down by
endo‐ amylases.
If their size is below the renal threshold, they are excreted.
Excretion of smaller particles continuously reduces osmotic
effectiveness of infused solution.
Molecular weight
Low MW solutions have more molecules per volume.
This gives them a greater oncotic effect.

Also gives them less persistence in plasma
Molar Substitution
This is where the drugs derive their name
0.6 = Hexastarch
0.5 = Pentastarch
0.4 = Tetrastarch
Molar Substitution
Proportion of the carbon atoms that are hydroxyethylated.
Expressed as a number from 0 to 1.
Most starches are substituted in the C2 or C6 position
Hydroxyethylation inhibits rate of destruction of starch polymer
by amylase
C2:C6 ratio

Proportion of molecules that are hydroxyethylated
at the C2 vs C6 position.
A higher C2:C6 ratio results in longer intravascular half life.
Adverse effects of colloids

Hemostatic
Dermatologic
Renal
HEMOSTATIC EFFECT
HEMOSTATIC EFFECT

Seems to be more pronounced with the slowly degraded
starches.

Predominant effect is on vWF:VIII.
Some platelet effects, but these are non‐ significant
Multicenter randomized trial
Patients with severe sepsis
intensive insulin therapy or conventional insulin therapy

10% pentastarch HES 200/0.5 or modified Ringer’s lactate
for fluid resuscitation.

HES was harmful, and its toxicity increased with accumulating doses.
Methods
Randomized controlled trial
7000 patients admitted to an intensive care unit
Fluid resuscitation with
6% HES Voluven 130/0.4 or 0.9% sodium chloride

The primary outcome was death within 90 days.
Secondary outcomes included AKI and failure and treatment with
renal-replacement therapy.

Conclusions
No significant difference in 90-day mortality
between patients resuscitated with 6% HES (130/0.4) or saline.
More patients who received resuscitation with HES
were treated with renal-replacement therapy.
Limitation
observed rate of death was lower than predicted.
Exclusion of patients with intracranial hemorrhage
and those whom clinicians considered unlikely to survive,
Inclusion of patients who had undergone elective surgery.
Patients were recruited after admission to the ICU,
(when the requirements for fluid resuscitation are often
less than those for patients in the emergency
department or the operating room)
Multicenter randomized trial
Patients with severe sepsis
fluid resuscitation in the ICU
6% HES 130/0.42 (Tetraspan) or Ringer’s acetate

The primary outcome measure was
either death or end-stage kidney failure (dependence on dialysis) at 90 days after
randomization

CONCLUSIONS
Fluid resuscitation with HES 130/0.42 had an increased risk of death at day 90
and were more likely to require renal-replacement therapy
In all these studies
There was no/ little difference in
Resuscitation volume of
Colloid and Crystalloid
( 1:1 to 1:1.5)
methods
We randomly assigned patients admitted to the ICU
Fluid resuscitation with
4 percent albumin or normal saline .

The primary outcome measure was death from any cause during the 28-day
period after randomization.

conclusions
In patients in the ICU, use of either 4 percent albumin or normal saline for fluid
resuscitation results in similar outcomes at 28 days
Post hoc follow-up study of patients
with traumatic brain injury who were enrolled in SAFE study

Methods
For patients with traumatic brain injury
baseline characteristics from case-report forms, clinical
records, and CT scans were recorded
and vital status and functional neurologic outcomes were determined
24 months after randomization.

Conclusions
Fluid resuscitation
with albumin was associated with higher mortality rates
than was resuscitation with saline.
Recommendations and conclusions
We recommend not to use
HES with mw ≥200 kDa and/or degree of substitution ≥0.4
in patients with severe sepsis or risk of acute kidney injury
and suggest not to use 6% HES 130/0.4 or gelatin
in these populations.

We recommend not to use colloids in patients with head injury
and not to administer gelatins and HES in organ donors.
We suggest not to use hyperoncotic solutions for fluid resuscitation.
We conclude and recommend that any new colloid should be introduced into clinical practice
only after its patient-important safety parameters are established
1. Crystalloids as the initial fluid of choice in the resuscitation of severe sepsis and
septic shock (grade 1B).
2. Against the use of hydroxyethyl starches for fluid resuscitation of severe sepsis and
septic shock (grade 1B).
3. Albumin in the fluid resuscitation of severe sepsis and septic shock when patients
require substantial amounts of crystalloids (grade 2C).
JAMA 2013
Effects of Fluid Resuscitation With Colloids vs Crystalloids on Mortality in Critically
Ill Patients Presenting With Hypovolemic ShockThe CRISTAL Randomized Trial
Djillali Annane, MD, for the CRISTAL Investigators

Colloids ( gelatins, dextrans, hydroxyethyl starches, or 4% or 20% of albumin)
Vs
crystalloids (isotonic or hypertonic saline or Ringer lactate solution)

Conclusions
No significant difference in 28-day mortality.
Although 90-day mortality was lower among patients receiving colloids,
this finding should be considered exploratory and
requires further study before reaching conclusions about efficacy.
Evidence Based Medicine
Involves caring for patients based upon
explicit integration of pathophysiology, clinical experience

And the
best available evidence,
adapted to each individual and the local health care setting

Luciano Gattinoni
So
Evidence Based Medicine
Should not kill
the
Medical Reasoning
Luciano Gattinoni
“The world is a dangerous place, not because of those who do
evil, but because of those who look on and do nothing.”
Albert Einstein

“You are not only responsible for what you say, but also for what you
do not say.”
Martin Luther King

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Colloid vs Crystalloids

  • 1. Colloid Solutions To Use or not to Use? Ubaidur Rahaman Associate Consultant Critical Care Medicine Fortis Flt. Lt. Rajan Dhall Hospital New Delhi 110070
  • 2. “the LV volume is a surrogate for LV wall tension And the LV wall tension a surrogate for LV stroke volume And the LV stroke volume determines CO And the LV CO is a surrogate for tissue blood flow And tissue blood flow is a surrogate for tissue oxygenation And the tissue oxygenation is a surrogate for ATP generation And ATP generation powers cellular function”
  • 5. SYNTHETIC COLLOIDS 10% Pentaspan 250/0.45 6% Hespan 450/0.60 6% Voluven 130/0.40
  • 6. Classification of Strarch Concentration Molecular weight Degree of substitution C2:C6 ratio
  • 7. Concentration= Oncocity Plasma- 25 mmHg 10% Pentaspan- 80 mmHg 6% Voluven- 26 mmHg
  • 8. Molecular weight HES are polydispersible substances. They contain a distribution of molecular weights. The number on the package is the average
  • 9. Molecular weight After infusion the molecules are broken down by endo‐ amylases. If their size is below the renal threshold, they are excreted. Excretion of smaller particles continuously reduces osmotic effectiveness of infused solution.
  • 10. Molecular weight Low MW solutions have more molecules per volume. This gives them a greater oncotic effect. Also gives them less persistence in plasma
  • 11. Molar Substitution This is where the drugs derive their name 0.6 = Hexastarch 0.5 = Pentastarch 0.4 = Tetrastarch
  • 12. Molar Substitution Proportion of the carbon atoms that are hydroxyethylated. Expressed as a number from 0 to 1. Most starches are substituted in the C2 or C6 position Hydroxyethylation inhibits rate of destruction of starch polymer by amylase
  • 13. C2:C6 ratio Proportion of molecules that are hydroxyethylated at the C2 vs C6 position. A higher C2:C6 ratio results in longer intravascular half life.
  • 14. Adverse effects of colloids Hemostatic Dermatologic Renal
  • 16. HEMOSTATIC EFFECT Seems to be more pronounced with the slowly degraded starches. Predominant effect is on vWF:VIII. Some platelet effects, but these are non‐ significant
  • 17.
  • 18. Multicenter randomized trial Patients with severe sepsis intensive insulin therapy or conventional insulin therapy 10% pentastarch HES 200/0.5 or modified Ringer’s lactate for fluid resuscitation. HES was harmful, and its toxicity increased with accumulating doses.
  • 19.
  • 20.
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  • 23. Methods Randomized controlled trial 7000 patients admitted to an intensive care unit Fluid resuscitation with 6% HES Voluven 130/0.4 or 0.9% sodium chloride The primary outcome was death within 90 days. Secondary outcomes included AKI and failure and treatment with renal-replacement therapy. Conclusions No significant difference in 90-day mortality between patients resuscitated with 6% HES (130/0.4) or saline. More patients who received resuscitation with HES were treated with renal-replacement therapy.
  • 24.
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  • 26.
  • 27. Limitation observed rate of death was lower than predicted. Exclusion of patients with intracranial hemorrhage and those whom clinicians considered unlikely to survive, Inclusion of patients who had undergone elective surgery. Patients were recruited after admission to the ICU, (when the requirements for fluid resuscitation are often less than those for patients in the emergency department or the operating room)
  • 28.
  • 29. Multicenter randomized trial Patients with severe sepsis fluid resuscitation in the ICU 6% HES 130/0.42 (Tetraspan) or Ringer’s acetate The primary outcome measure was either death or end-stage kidney failure (dependence on dialysis) at 90 days after randomization CONCLUSIONS Fluid resuscitation with HES 130/0.42 had an increased risk of death at day 90 and were more likely to require renal-replacement therapy
  • 30.
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  • 33. In all these studies There was no/ little difference in Resuscitation volume of Colloid and Crystalloid ( 1:1 to 1:1.5)
  • 34.
  • 35. methods We randomly assigned patients admitted to the ICU Fluid resuscitation with 4 percent albumin or normal saline . The primary outcome measure was death from any cause during the 28-day period after randomization. conclusions In patients in the ICU, use of either 4 percent albumin or normal saline for fluid resuscitation results in similar outcomes at 28 days
  • 36.
  • 37.
  • 38. Post hoc follow-up study of patients with traumatic brain injury who were enrolled in SAFE study Methods For patients with traumatic brain injury baseline characteristics from case-report forms, clinical records, and CT scans were recorded and vital status and functional neurologic outcomes were determined 24 months after randomization. Conclusions Fluid resuscitation with albumin was associated with higher mortality rates than was resuscitation with saline.
  • 39.
  • 40. Recommendations and conclusions We recommend not to use HES with mw ≥200 kDa and/or degree of substitution ≥0.4 in patients with severe sepsis or risk of acute kidney injury and suggest not to use 6% HES 130/0.4 or gelatin in these populations. We recommend not to use colloids in patients with head injury and not to administer gelatins and HES in organ donors. We suggest not to use hyperoncotic solutions for fluid resuscitation. We conclude and recommend that any new colloid should be introduced into clinical practice only after its patient-important safety parameters are established
  • 41. 1. Crystalloids as the initial fluid of choice in the resuscitation of severe sepsis and septic shock (grade 1B). 2. Against the use of hydroxyethyl starches for fluid resuscitation of severe sepsis and septic shock (grade 1B). 3. Albumin in the fluid resuscitation of severe sepsis and septic shock when patients require substantial amounts of crystalloids (grade 2C).
  • 42. JAMA 2013 Effects of Fluid Resuscitation With Colloids vs Crystalloids on Mortality in Critically Ill Patients Presenting With Hypovolemic ShockThe CRISTAL Randomized Trial Djillali Annane, MD, for the CRISTAL Investigators Colloids ( gelatins, dextrans, hydroxyethyl starches, or 4% or 20% of albumin) Vs crystalloids (isotonic or hypertonic saline or Ringer lactate solution) Conclusions No significant difference in 28-day mortality. Although 90-day mortality was lower among patients receiving colloids, this finding should be considered exploratory and requires further study before reaching conclusions about efficacy.
  • 43. Evidence Based Medicine Involves caring for patients based upon explicit integration of pathophysiology, clinical experience And the best available evidence, adapted to each individual and the local health care setting Luciano Gattinoni
  • 44. So Evidence Based Medicine Should not kill the Medical Reasoning Luciano Gattinoni
  • 45. “The world is a dangerous place, not because of those who do evil, but because of those who look on and do nothing.” Albert Einstein “You are not only responsible for what you say, but also for what you do not say.” Martin Luther King