Plasma expanders

Types

1. Natural colloids
   • Human albumin: 5%, 20%, or 25%
   • Plasma protein fraction
   • Fresh frozen plasma, used primarily when coagulation factors are also needed
2. Synthetic colloids
   • Dextrans
     • Dextran 40, usually 10% solution
     • Dextran 70, usually 6% solution
   • Gelatin preparations: polygeline, succinylated gelatin
   • Hydroxyethyl starches (HES)
3. Crystalloids used for volume resuscitation
   • 0.9% sodium chloride
   • Ringer lactate/Hartmann solution
   • Balanced salt solutions

Dextran: pharmacology

1. Source and chemistry

• Dextran is a high-molecular-weight, branched polysaccharide made of glucose units.
• It is produced by bacterial action, classically Leuconostoc mesenteroides, on sucrose.
• It is administered only by intravenous infusion.
• It acts as a synthetic colloid, remaining mainly within the intravascular compartment and exerting colloid osmotic pressure.

2. Preparations

Dextran 40

• Also called low-molecular-weight dextran or rheomacrodex.
• As a 10% solution, it is hyperoncotic and draws water from the interstitial space into blood vessels.
• It is eliminated more rapidly through the kidney because of its lower molecular weight.
• It can improve microcirculatory flow by reducing blood viscosity and red cell aggregation.

Dextran 70

• Also called macrodex.
• Used as a 6% solution.
• Its volume expansion is somewhat greater than the infused volume.
• Due to its larger molecular size, intravascular volume expansion may persist for up to about 48 hours. - Mulholland and Greenfield's Surgery, p. 558

3. Mechanism of action

1. Increasing colloid osmotic pressure
   • Retains infused fluid in the vascular compartment.
   • Dextran 40, being hyperoncotic, additionally mobilizes interstitial fluid into the circulation.
2. Increasing venous return and cardiac output
   • Improved circulating volume increases preload, tissue perfusion, and blood pressure in hypovolaemia.
3. Haemodilution
   • Reduces blood viscosity.
4. Improving microcirculation
   • Dextran 40 reduces red cell aggregation and improves capillary blood flow.
   • Useful in hyperviscosity states and peripheral vascular disease.
5. Antithrombotic effects
   • Decreases platelet adhesiveness.
   • Reduces platelet function.
   • Reduces factor VIII and von Willebrand factor activity.
   • Interferes with fibrin-network formation and promotes fibrin degradation.

4. Pharmacokinetics

• Given intravenously.
• Large molecules remain in plasma initially.
• Smaller dextran fractions are filtered by glomeruli and excreted in urine.
• Some dextran is taken up by the reticuloendothelial system and metabolized slowly.
• Dextran 40 is cleared faster than dextran 70.

5. Therapeutic uses

A. Plasma volume expansion

• Hypovolaemic shock due to haemorrhage, burns, surgery, or trauma
• Perioperative volume replacement
• Extracorporeal circulation, as a pump-priming fluid

B. Improvement of microcirculation

• Peripheral vascular disease
• Hyperviscosity syndromes
• Prevention of vascular stasis in selected settings

C. Thromboembolism prophylaxis

• Dextran 40 has been used to reduce postoperative venous thrombosis and pulmonary embolism, for example after high-risk orthopaedic procedures.
• Its use for this purpose is limited by bleeding and anaphylactoid risks.

D. Microvascular surgery

• Used historically to maintain graft or flap patency because of its antiplatelet and rheological effects.
• Current use is limited, and evidence does not support routine administration in free-flap surgery. - Cummings Otolaryngology Head and Neck Surgery, lines 1109-1117

6. Adverse effects

1. Anaphylactoid or allergic reactions

• Urticaria, flushing, itching
• Bronchospasm, wheeze, chest tightness
• Hypotension and shock
• Rarely cardiac arrest

2. Bleeding tendency

• Inhibits platelet adhesiveness and function
• Lowers factor VIII and von Willebrand factor activity
• Causes haemodilution of coagulation factors and platelets

3. Volume overload

• Pulmonary oedema
• Worsening heart failure
• Hypertension or circulatory congestion

4. Renal effects

• Osmotic nephrosis-like renal tubular injury may occur, particularly with large doses of dextran 40.
• Oliguria and acute kidney injury can occur in susceptible patients.

5. Interference with blood grouping and cross-matching

• Dextran may interfere with blood typing and cross-matching.
• Hence, blood samples for grouping and cross-matching should be obtained before dextran administration.

6. Other effects

• Haemodilution with reduced haematocrit and plasma protein concentration
• Fever, phlebitis, local infusion reactions
• Rare acute respiratory distress syndrome

7. Contraindications

• Known dextran hypersensitivity
• Severe haemostatic defects, thrombocytopenia, hypofibrinogenaemia
• Active bleeding or major bleeding risk
• Patients on anticoagulants when bleeding risk is significant
• Severe renal impairment, oliguria, or anuria
• Marked cardiac decompensation or pulmonary oedema
• Severe fluid overload states

8. Precautions

• Obtain blood grouping and cross-matching samples before infusion.
• Monitor pulse, blood pressure, urine output, oxygenation, haematocrit, coagulation profile, and signs of fluid overload.
• Use cautiously in renal impairment, cardiac failure, and elderly patients.
• Stop the infusion immediately if hypersensitivity, bronchospasm, hypotension, or bleeding develops.
• Dextran should not be mixed indiscriminately with other drugs in the infusion container.

9. Key comparison