Plasma volume expanders

Pharmacology of Plasma volume expanders

1. Dr. Ajay Kumar M. Pharm., Ph.D. 1

2. BODY FLUID COMPARTMENTS 2 TBW: 60% of body weight (42L) ICF : - 40% of body weight (28L) - 2/3 rd ofTBW ECF: 20% of body weight (14L) Interstitial fluid (15% of body weight, 11L) Blood plasma (5% of body weight, 3L) 75 to 80% ECF is in interstitial fluid

3. 1. Blood is a fluid connective tissue that circulate continuously around the body. 2. Plasma is a clear, straw coloured, wat e ry fl u id in whi c h s e v e r a l d i f fe r ent types of blood cells are suspended ( plasma is blood devoid of blood cells). 3. Serum is plasma without clotting factors 3

4. DISTRIBUTION OF ELECTROLYTES AND SUBTANCES IN BODY FLUIDS 4 SUBSTANCE PLASMA (mOsm/L H2O) INTERSTITIAL ( mOsm/L H2O) INTRACELLULA R (mOsm/L H2O) Na+ 142 139 14 K+ 4.2 4 140 Ca++ 1.3 1.2 1 Cl- 108 108 4 HCO3- 24 28.3 10 Amino acid 2 2 8 Lactate 1.2 1.2 1.5 Glucose 5.6 5.6 0-20 mg/dL

5. Volume Expanders 5 Volume expanders are the intravenous fluid solutions that are used to increase or retain the volume of fluid in the circulating blood. Generally volume expanders are used to replace fluids that are lost due to illness , trauma or surgery . The y do not carry oxygen .

6. Types of volume expanders 6 There are two main types of volume expanders: 1 . Cr y sta l l o i d s : cr y s t al l oi d s ar e aq u eo u s sol u t i o n s of m i ner al s a l t s or o t he r w a t er - sol u b l e mo l e cul e s e . g . nor mal saline, dextrose, Ringer’s solution etc. 2. Colloids : Colloids are larger insoluble molecules , such as dextran , human albumin, gelatin , blood. Blood itself is a colloid.

7. Colloids are better than Crystalloids because : 7  The larger molecules of colloids are retained more easily in the intravascular space & increase osmotic pressure .  So, more effective resuscitation of plasma volume occurs by colloids than produced by that of crystalloids.  Duration of action is relatively longer than c rystalloids .

8. Ideal properties of PVEs . 8  Iso-oncotic with plasma  Distributed to intravascular compartment o nly  Pharmacodynamically inert  Non-pyrogenic, non-allergenic & non- antigenic  No interference with blood grouping or cross-matching  Stable, easily sterilizable and cheap.

9. Colloidal Plasma expanders 9  Human albumin  Dextran  Degraded gelatin polymer (Polygeline)  Hydroxyethyl starch (Hetastarch/HES)  Polyvinyl pyrrolidone (PVP)

10. Mechanism of action: 10 Generally works on the principle of osmosis . Increases Plasma osmotic pressure, drawing water into plasma from interstitial fluid. Since the lost blood is replaced with a suitable fluid , the now diluted blood flows more easily, even in small vessels. As a result of chemical changes, more oxygen is released to the tissues.

11. Important points 11 - replace fluid to increase volume as RBCs still sufficient to supply oxygen. Molecular weight of colloids determine their duration of action and ability to expand blood volume. Dextran , HMW starch have negative impact on coagulation, may induce acute renal failure, allergy. Colloids classification- a)natural-albumin b)synthetic- gelatin, H ES , PVP

12. The Natural Colloid—Human Albumin 12 - most abundant protein in human plasma (40-50 g/L), with a total body content of 4 to5 g/kg. - hydrophilic, nonglycosylated protein with a molecular weight of 69 kDa. distributed one third to two thirds in the intravascular compartment relative to the extravascular compartment, and accounts for 70% to 80% of the plasma colloid oncotic pressure (COP) - capacity to bind cations, anions, and toxins , such as bilirubin, gives it an important physiological role in buffering the acid-base balance of the blood, in regulating the ionized fraction of cations including calcium and magnesium, and in scavenging free radicals and transporting proteins and drugs. synthesized in the liver with a mean half-life of 14.8 days and is degraded mostly in muscle, the liver, and the kidney. Hypoalbuminemia from a range of pathologies is a poor prognostic factor.

13. 1.Human Albumin 13 is  It is obtained from pooled human plasma. ( Edwin Cohn’s development of a method to isolate albumin in a safe and stable form from human plasma)  It can be used without regard to patient’s blood group and doesn’t interfere with coagulation.  It is free of risk of transmission of hepatitis because the preparation heat treated. - Still first line

14. Co n t d… 14  Crystalloid solution must be infused concurrently for optimum benefit.  It has been used in acute hypo p rotei n aemia , acut e liver failure and dialysis.  It is comparatively expensive .  Available products: Albudac, Albupan 50, 100 ml inj., Albumed 5%, 20% infusion (100 ml)

15. Albumin contd.. 15 available as iso-oncotic (4%-5%) solutions for intravascular volume expansion and as hyperoncotic solutions (20%-25%) for the maintenance of fluid balance between compartments and the restoration of COP. albumin’s position as the benchmark biological therapy in terms of pathogen safety remains unchallenged . -as an additive stabilizer for other therapeutics such as recombinant proteins and monoclonal antibodies , and the so-called “new generation” formulations of these therapies, which exclude albumin in the context of enhanced safety are addressing perception rather than real risk.

16. Dextrans 16 are groups of branched polysaccharides derived from sucrose( beet root) by the action of the bacterium Leuconostoc mesenteroides. different dextran preparations are polydisperse mixtures grouped on the basis of their average molecular weight, which is different from the average molecular weight of the particles with colloid oncotic power, which is important for their hemodynamic action. main types are dextran 40, available as a 10% solution, and dextran 60 and 70, prepared as a 6% solution . molecular weight is the chief determinant of the pharmacodynamics.

17. a) Dextran 70 17 It is most commonly used preparation . It expands plasma volume for nearly 24 hrs . Excreted slowly by glomerular filtration as well as oxidized in body over weeks . and some amount is deposited in retuculo- endothelial cells.

18. Dextran 70 has nearly all the properties of an ideal plasma except: 18  It may interfere with blood grouping and cross matching .  It can interfere with coagulation and platelet function and thus prolong bleeding time .  Some polysaccharide reacting antibodies, if present, may cross react with dextran and trigger anaphylactic reaction like Urticaria, itching, bronchospasm, fall in BP.

19. b) Dextran 40 19 It acts more rapidly than dextrose 70 . It reduces blood viscosity . It is excreted through renal tubules and occasionally may produce acute renal failure. The total dose should not exceed 20 ml/kg in 24 h r. Dextrans can be stored for 10 years and are cheap so are the most commonly used plasma expanders . Caution: Dextran doesn’t provide necessary electrolytes and can cause hyponatremia or other electrolyte disturbances.

20. 3. Degraded gelatin polymer (polygeline ) 20  It is synthetic polymer (polypeptide) of MW-30,000 .  It doesn’t interfere with blood grouping a nd cross matching and is non-antigenic .  Expands plasma volume for 12 hrs.  It is more expensive than dextran and can also be used for priming of heart-lung and dialysis m achines .  Brands: Haemaccel; Seraccel 500 ml vaccine.

21. Gel a tin 21 Gelatins are manufactured from bovine gelatin, a derivative of collagen, which is cross-linked, urea linked, or succinylated to yield the final products. The molecular weight ranges from 30 kDa to 35 kDa, and

22. 4. Hydroxyethyl s t a r ch ( H e t a st a r ch) 22 It is a complex mixture of ethoxylated amylopectin of various molecular sizes; average MW 4.5 lacs. It maintains blood volume longer. No coagulation disturbances . It improves hemodynamic status for 24 hrs.

23. H e t a s t a r c h c o n t d.. 23  Adverse effects: Vomiting, mild fever, itching, chills, flu like symptoms, swelling of salivary glands, Urticaria, bronchospasm etc.  Brand: Expan 6% inj (100 , 500 ml vac) It has also been used to improve harvesting of granulocytes because it accelerates erythrocyte sedimentation. Adverse effects: Anaphylactic reactions, mild fever, chilling, periorbital edema, Urticaria, itching .

24. 5 . Polyvinylpyrrolidine ( PVP) 24  It is a synthetic polymer of average MW 40,000 used as a 3.5 % solution.  PVP was used as blood plasma expander for trauma victims after the 1950s.  It interferes with blood grouping and cross matching and is histmine releaser .  It binds to penicillin and Insulin.

25. Co n t d 25  I . t is excreted by kidney and small amounts by liver into bile.  A fraction is stored in RE cells f or prolonged periods.  It is less commonly used plasma expander .

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