Plasma volume expanders

to increase plasma volume as in shock

1. Plasma Volume Expanders By Dr. Alka Bansal Associate Professor, Department of Pharmacology, SMS Medical College, Jaipur

2. BODY FLUID COMPARTMENTS TBW: 60% of body weight (42L) ICF: - 40% of body weight (28L) - 2/3 rd of TBW 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. Blood is a fluid connective tissue that circulate continuously around the body . Plasma is a clear, straw coloured , watery fluid in which several different types of blood cells are suspended ( plasma is blood devoid of blood cells). Serum is plasma without clotting factors

4. DISTRIBUTION OF ELECTROLYTES AND SUBTANCES IN BODY FLUIDS SUBSTANCE PLASMA (mOsm/L H2O) INTERSTITIAL (mOsm/L INTRACELLULAR H2O) (mOsm/L H2O) Na+ 142 1 39 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  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 . They do not carry oxygen .

6. Types of volume expanders There are two main types of volume expanders: Crystalloids : crystalloids are aqueous solutions of mineral salts or other water-soluble molecules . E.g. normal saline, dextrose, Ringer’s solution etc. 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:  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 crystalloids .

8. Ideal properties of PVEs .  Iso-oncotic with plasma  Distributed to intravascular compartment only  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 -  Human albumin  Dextran  Degraded gelatin polymer (Polygeline)  Hydroxyethyl starch (Hetastarch/HES)  Polyvinyl pyrrolidone (PVP)

10. Mechanism of action: 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 - 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, HES, PVP

12. The Natural Colloid—Human Albumin - 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  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 is heat treated . - Still first line St. of Albumin

14. Cont d …  Crystalloid solution must be infused concurrently for optimum benefit.  It has been used in acute hypoproteinaemia, acute 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.. 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 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 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:  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   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 hr.  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)  It is synthetic polymer (polypeptide) of MW-30,000.  It doesn’t interfere with blood grouping and 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 machines .  Brands: Haemaccel; Seraccel 500 ml vaccine.

21. Gelatin 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 starch(Hetastarch) ulati o n  It is a complex mixture of ethoxylated amylopectin of various molecular sizes; average MW 4.5 lacs.  It maintains blood volume lon ger .  It doesn’t cause acute renal failure or coag ulation disturbances .  It improves hemodynamic status for 24 hrs.

23. Hetastarch contd..  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)  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. Contd….  It is excreted by kidney and small amounts by liver into bile.  A fraction is stored in RE cells for prolonged periods.  It is less commonly used plasma expander. Sample of PVP

26. Other uses of PVP:  PVP is also used in personal care products such as shampoos and toothpaste, hair sprays and gels.  It is used as binder in many p harmaceutical tablets.  PVP added to Iodine forms a complex called Povidone- Iodine that posses disinfectant properties. And known under the trade name of Betadine and Pyodine.

27. A/E of the Synthetic Colloids Coagulopathy , renal failure, and circulatory and hepatic complications . Volume substitution with fluids other than fresh blood may be expected to lead to a progressive dilution of the cellular and protein hemostatic components. This occurs for the anticoagulant as well as the procoagulant proteins, and monitoring with the thromboelastogram (TEG) shows that acute hemodilution with saline induces a hypercoaguable state of probably because of the dilution of antithrombin III (ATIII), the most important physiological anticoagulant, which has a high normal range (plasma levels of 80%-120%). Hemodilution , as a result of albumin infusion , leads to in vitro coagulation abnormalities at 30% volume replacement, but is not considered to have clinically significant effects.

28. A/E contd -- Gelatin has induced postoperative hypercoagulation following joint replacement surgeryand results in decreased TEG-measured clot strength.It also impaired platelet aggregation i n normal volunteers and during cardiac surgery Dextran and HES molecules exert an effect on both primary hemostasis and coagulation through a drop in the factor VIII/ von Willebrand factor (FVIII/VWF) complex , which is higher than predicted through dilution The incidence of acute renal failure associated with dextran and HES has been reported .

29. CRYSTALLOIDS Crystal + oid (resembling a crystal) Electrolyte solutions with small molecules that can diffuse freely throughout the extracellular space Relatively low tendency to stay intravascular Principal component is inorganic salt sodium chloride (NaCl) 75-80% of infused crystalloid is distributed in interstitial space Volume resuscitation with crystalloid fluids expand interstitial volume rather than plasma volume Eg: Isotonic saline, Lactated Ringer’s solution, etc.,

30. TYPES OF CRYSTALLOIDS Isotonic crystalloids : When the concentration of the particles (solutes) is similar to that of plasma, it doesn't move into cells and remains within the extracellular compartment thus increasing intravascular volume. Eg: 0.9% NaCl, Ringer’s lactate, D5W Hypotonic solutions : Compared with intracellular fluid (as well as compared with isotonic solutions ), hypotonic solutions have a lower concentration of solutes (electrolytes). These solutions will hydrate cells , although their use may deplete fluid within the circulatory system. Eg: 0.45% sodium chloride (0.45% NaCl), 0.33% sodium chloride, 0.2% sodium chloride, and 2.5% dextrose in water Hypertonic solutions : Solution that have a higher tonicity or solute concentration. The osmotic pressure gradient draws water out of the intracellular space, increasing extracellular fluid volume, so they are used as volume expanders . Eg : 3% NaCl, D5NS

31. FLUID Na+ Cl- K+ Ca++ pH GLUCOSE BUFFER O S MO LA R ITY TONICITY TYPICAL I N D I C A TI O N N ORMAL PLASMA 1 4 2 108 4.2 1.3 7.4 ~0.85 HCO3- ~24 mEq/L ~290 N/A N/A N ORMAL SALINE 154 154 5.7 308 Isotonic Resuscitation RINGER’S LACTATE 1 30 109 4 3 6.4 Lactate 28 mEq/L 273 Isotonic Resuscitation D5W 50 252 Hypotonic Hypernatremia, Hypoglycemia

32. ISOTONIC SALINE (Normal saline/NS) Prototype crystalloid fluid is 0.9% NaCl 9 grams of NaCl per liter It's called "normal saline solution" because the percentage of sodium chloride in the solution is approximate to the concentration of sodium and chloride in the intravascular space. Osmolarity = 308 mOsm/L

33. WHEN TO BE GIVEN? To treat low extracellular fluid as in fluid volume deficit from h emorrhage , Severe vomiting or diarrhea, Heavy drainage from GI suction Shock Mild hyponatremia Metabolic acidosis (such as diabetic ketoacidosis) It’s the fluid of choice for resuscitation efforts . It's the only fluid used with administration of blood products. DISADVANTAGE:- Metabolic acidosis – due to high chloride concentration (Hyperchloremic acidosis) Intraoperative infusion of isotonic saline at the rate of 30 ml/kg/h causes a drop in serum pH from 7.41 to 7.28 after 2 hours

34. RINGER’S LACTATE (HARTMANN’S SOLUTION) FEATURES :- K+ and Ca++ ion concentration are in appropriate concentrations of plasma Na+ concentration is reduced for electrical neutrality Lactate addition requires reduction in chloride concentration which is a close approximation of plasma chloride concentration Thus the risk of hyperchloremic acidosis with large volume infusion of RL is eliminated . It is contraindicated as diluents for blood transfusions

35. USES:- The most physiologically adaptable fluid because its electrolyte content is most closely related to the composition of the body's blood serum and plasma. Another choice for first-line fluid resuscitation for certain patients, such as those with burn injuries. When to be used? To replace GI tract fluid losses ( Diarrhea or vomiting ) Fluid losses due to burns and trauma Patients experiencing acute blood loss or hypovolemia

36. DISADVANTAGES:- Ca++ in RL can bind with certain drugs and inactivate or reduce their effectiveness Drugs to be not Ii nfused with R L are : Aminocaproic acid Amphotericin , ampicillin , thiopentone RL is metabolized in the liver, which converts the lactate to bicarbonate . RL is administered to patients who have metabolic acidosis not patients with lactic acidosis Not given to patients with liver disease as they can't metabolize lactate

37. D5W (5% of dextrose in water) 1 gram dextrose = 3.4 kcal  50 grams = 170 kcal/L Osmolarity = 252 mOsm/L It is considered an isotonic solution, but when the dextrose is metabolized, the solution actually becomes hypotonic and causes fluid to shift into cells. <10% of infused volume of D5W remains intravascularly 2/3 rd of infused volume ends up inside cells Predominant effect is cellular swelling

38. How does it work? D5W provides free water that pass through membrane pores to both intracellular and extracellular spaces. Its smaller size allows the molecules to pass more freely between compartments , thus expanding both compartments simultaneously It provides 170 calories per liter, but it doesn't replace electrolytes . The supplied calories doesn't provide enough nutrition for prolonged use . Uses - hypernatremia and hypoglycemia

39. DISAVANTAGES:- D5W is not good for patients with renal failure or cardiac problems since it could cause fluid overload . patients at risk for intracranial pressure should not receive D5W since it could increase cerebral edema D5W shouldn't be used in isolation to treat fluid volume deficit because it dilutes plasma electrolyte concentrations Never mix dextrose with blood as it causes blood to hemolyze. Not used for resuscitation , because the solution won't remain in the intravascular space.