Colloid SolutionsTo Use or not to Use?

Ubaidur RahamanAssociate Consultant Critical Care Medicine

Fortis Flt. Lt. Rajan Dhall HospitalNew 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

SYNTHETICGelatinStarch

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 = Hexastarch0.5 = Pentastarch0.4 = 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 trialPatients with severe sepsis

intensive insulin therapy or conventional insulin therapy

HES was harmful, and its toxicity increased with accumulating doses.

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

MethodsRandomized controlled trial

7000 patients admitted to an intensive care unitFluid resuscitation with

6% HES Voluven 130/0.4 or 0.9% sodium chloride

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.

The primary outcome was death within 90 days.Secondary outcomes included AKI and failure and treatment 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 emergencydepartment or the operating room)

Multicenter randomized trialPatients with severe sepsis

fluid resuscitation in the ICU 6% HES 130/0.42 (Tetraspan) or Ringer’s acetate

CONCLUSIONSFluid resuscitation with HES 130/0.42 had an increased risk of death at day 90

and were more likely to require renal-replacement therapy

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

randomization

In all these studiesThere was no/ little difference in

Resuscitation volume of Colloid and Crystalloid

( 1:1 to 1:1.5)

methodsWe randomly assigned patients admitted to the ICU

Fluid resuscitation with 4 percent albumin or normal saline .

conclusionsIn patients in the ICU, use of either 4 percent albumin or normal saline for fluid

resuscitation results in similar outcomes at 28 days

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

MethodsFor patients with traumatic brain injury

baseline characteristics from case-report forms, clinicalrecords, and CT scans were recorded

and vital status and functional neurologic outcomes were determined24 months after randomization.

Post hoc follow-up study of patientswith traumatic brain injury who were enrolled in SAFE study

ConclusionsFluid resuscitation

with albumin was associated with higher mortality rates than was resuscitation with saline.

Recommendations and conclusionsWe 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 injuryand 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).

Effects of Fluid Resuscitation With Colloids vs Crystalloids on Mortality in Critically Ill Patients Presenting With Hypovolemic ShockThe CRISTAL

Randomized TrialDjillali Annane, MD, for the CRISTAL Investigators

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.

JAMA 2013

Colloids ( gelatins, dextrans, hydroxyethyl starches, or 4% or 20% of albumin) Vs

crystalloids (isotonic or hypertonic saline or Ringer lactate solution)

Involves caring for patients based upon explicit integration of pathophysiology, clinical experience

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

Evidence Based Medicine

And the

Luciano Gattinoni

SoEvidence 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