This document summarizes different types of plasma expanders used to treat conditions involving fluid loss such as hemorrhage and shock. There are two main types of volume expanders: crystalloids like saline and colloids made from large insoluble molecules such as dextran, albumin, and gelatin. Common colloid plasma expanders discussed include albumin from human plasma, gelatins produced from collagen, hydroxyethyl starches, dextrans made by bacteria, and hypertonic saline solutions. The document compares the characteristics, mechanisms, and side effects of these different plasma expander options.

1. PHARMACOLOGY
OF
PLASMA EXPANDERS
KOPPALA RVS CHAITANYA

2. PLASMA EXPANDERS
• Plasma expanders are the agents with high molecular weight and boost the
plasma volume by increasing osmatic pressure
• They are use to treat patients who suffered from heamorrhage and shock
• Generally used to replace the fluids that are lost due to illness, trauma and
surgery
• These are used to correct Hyppovolaemia due to loss of plasma and blood.

3. PLASMA EXPANDERS
• Plasma expanders are hyperoncotic and/or hypertonic fluids that expand
the circulating blood volume more than isotonic/iso- oncotic fluids.
• Typically, colloidal solutions are used.
• However, hypertonic crystalloid solutions also provide short-term plasma
expansion.

4. TYPES OF PLASMA EXPANDERS
There are two main types of volume expanders
1. Crystolloids: crystalloids are aqueous solutions of mineral Salts
or other water soluble molecules ex: Normal saline , dextrose and
Ringers solution
2. Colloids : Colloids are large insoluble molecules such as Dextran
, Human albumin, Gelatin, Blood.
Blood itself is a colloid

5. • Colloids are a dispersion of organic molecules of variable molecular weights
held in solution by polar, covalent bonds that attract water molecules.
• These large organic molecules do not cross the vascular endothelium easily,
thus exerting a colloid osmotic pressure (COP), which attracts extravascular
fluid into the circulation.
• Compared with weight-averaged molecular weight (MWw; arithmetic
mean) the number-averaged molecular weight (MWn; median) of a plasma
expander correlates more closely with duration of action.
• In contrast, COP is proportional to the number of molecules or ions of
solute.

6. PROTEIN COLLOIDS
ALBUMIN
• Albumin is a naturally occurring plasma protein.
• Human albumin solution (HAS) contains 96% albumin, whilst a purified protein
fraction contains 83% albumin, with the remainder as globulin.
• Albumin is derived from pooled human plasma, serum or normal placentas, and then
sterilized by heating and ultrafiltration to prevent disease transmission.
• Albumin solutions prepared from whole blood contain no clotting factors, blood
group antibodies or plasma cholinesterases; therefore, blood grouping is not required.

7. • The MWw and MWn of HAS are approximately 69 kDa.
• Isotonic (4e5% protein) and concentrated solutions (20e25%) are
available.
• Infusion of 100 ml 25% HAS increases the intra- vascular volume by 450
ml, but this expansion depends on blood volume, serum protein
concentration, capillary permeability and extravascular water availability.
• HAS confers no advantage over saline in the resuscitation of critically ill
patients and should not be used in this context.
• Side effects of HAS are very rare; the incidence of anaphylactoid
reactions is approximately 1/1000 per year.

8. GELATINS
• Gelatins are polypeptides (MWw 30e35 kDa) produced by hydrolysis of
bovine collagen.
• Further modification produces urea linked gelatins (Haemaccel),
succinylated gelatins (Gelofusine) and oxypolygelatins
• All pyrogen and preservative free.
• Gelatins are rapidly removed by glomerular filtration and protease
catabolism within the reticuloendothelial system (RES) and therefore
their intravascular half-life is short (1e3 hours).

9. • Gelofusine increases the time to peak clot strength formation in
whole blood by 77%, and reduces the rate of fibrin formation by
43% compared to controls.
• Platelet aggregation is also impaired.
• Severe anaphylactoid reactions occur more often with urea-linked
solutions (1/2000) compared with succinylated preparations
(1/13,000 per year).
• Gelatins do not cause renal dysfunction.

10. NON-PROTEIN, SYNTHETIC COLLOIDS
HYDROXYETHYLATED STARCH (HES)
• Hydroxyethylated starch (HES) is a branched natural polymer of
amylopectin which is rapidly hydrolysed in vivo by amylase.
• Therefore, HES molecules are stabilized by substituting
hydroxyethyl groups for hydroxyl groups at the C2, C3 and C6
position of the glucose residues.

11. • HES is available as 3, 6 and 10% solutions, with varying MWw: low
molecular weight (70 kDa), medium molecular weight (130e270 kDa)
and high molecular weight (HMW; >450 kDa).
• A high C2:C6 ratio and a high MS both prolong the duration of action of
HES.
• HES has a water-binding capacity of 20e30 ml/g.
• After hydrolysis, the resulting HES fragments are excreted renally
within24 hours.
• A small fraction enters the RES and interstitium.

12. • HES attenuates capillary leakage during the inflammatory response and restores
macrophage function after major haemorrhage.
• Additionally, starches improve microcirculatory oxygen flux by reducing blood viscosity.
• High-MS starch impairs coagulation by reducing the concentration of factor VIII:VIIIc
and von Willebrand factor (vWF).
• Platelet activity is hampered by blockade of the platelet fibrinogen receptor glycoprotein
IIb-IIIa.
• Smaller starch molecules and those with less MS produce negligible coagulation defects.
• Low-MS starch causes a latent, dose-dependent itch typically of the upper torso due to
tissue sequestration.
• The incidence of severe anaphylactoid reactions is less than 1/16,000.

13. • Much has been written on the propensity of starches to cause acute kidney injury.
• At the end of 2013, the Pharmacovigilance Risk Assessment Committee of the
European Medicines Agency reviewed the available evidence, which indicated
that starches were associated with an increased incidence of acute kidney injury
(AKI) and increased need for renal replacement therapy (RRT) in critically
unwell patients.
• Furthermore, the collated evidence indicated increased 90-day mortality in those
patients who had received starches. As a result, HES is not recommended for
critically unwell patients.
• A more recent meta-analysis did not find increased mortality or increased
incidence of AKI associated with perioperative HES administration in surgical
patients.
• However, the authors did not find any benefit of HES over crystalloid, and on
that basis could not recommend the use of HES in the surgical patient population.

14. DEXTRANS
• Dextrans are polysaccharides produced by the bacterium Leuconostoc mesenteroides
acting on sucrose.
• Acid hydrolysis and subsequent ethanol fractionation produce the final products:
dextran 40 (MWw ¼ 40 kDa) and dextran 70 (MWw ¼ 70 kDa).
• Dextran 40 and 70 bind 30 ml and 20e25 ml of water/g, respectively.
• The kidneys rapidly eliminate 70% of dextran 40 and 50% of dextran 70 unchanged,
whilst the remainder is metabolized to glucose.
• A small proportion of dextran enters the interstitium or is eliminated via the gut.
• The intravascular half-life is determined by particle size, with dextran 70 remaining
for 6 to 8 hours compared with 5 hours for dextran 40.

15. • Dextran produces similar microcirculatory effects to HES.
• Ischaemiae reperfusion injury is attenuated by a reduction of activated
leucocyte eendothelial interaction.
• Dextran 40 and dextran 70 solutions have similar effects on coagulation to
HES, which limits their use to 1.5 g/kg/day.
• In addition, dextran promotes fibrinolysis.
• Acute renal impairment caused by renal tubular obstruction has been
associated with dextran, particularly in hypovolaemia, oliguria or patients with
existing renal dysfunction.
• The incidence of severe anaphylactoid reactions is 1/4500 per year.

16. HYPERTONIC SALINE SOLUTIONS
• Hypertonic saline solutions rapidly mobilize extravascular fluid into the circulation by
their hypertonicity; approximately eightfold that of plasma.
• In severe head injury 250 ml 7.5% saline produces a significantly better improvement
in brain tissue oxygen tension, intra-cranial pressure, cerebral perfusion pressure, and
cardiac output when compared with 0.75 g/kg mannitol 25%.6
• However, the Resuscitation Outcomes Consortium stopped two pre-hospital trials of
hypertonic saline (NaCl) in haemorrhagic shock and severe head injury (without
shock) after interim analysis demonstrated no benefit with regard to 28-day survival.
• Hypertonic crystalloids produce a brief plasma expansion, and so they are mixed with
a colloid (e.g. 7.2% NaCl þ 6% HES 200 or 7.5% NaCl þ 6% dextran 70) to prolong
their duration of action.
• An infusion of 4 ml/kg in severe hypovolaemia (e.g. trauma, burns) has been
recommended.

19. ARTIFICIAL OXYGEN CARRIERS
• Plasma expanders do not transport oxygen.
• Haemoglobin- based oxygen carriers consist of stromal-free haemoglobin that
lacks 2,3-diphosphoglycerate and has a very high oxygen affinity.
• Modification of these oxygen carriers by polymerization, stabilization,
conjugation, hybridization or encapsulation has overcome these problems.
• Perfluorocarbon oxygen carriers consist of inert, organic molecules that dissolve
large volumes of gas.
• Unfortunately, they have a linear oxygen-binding capacity and a narrow
therapeutic index that can lead to oxygen toxicity.

20. Thank You