1. IV FLUIDS – COMPOSITION ;
INDICATION & SIDE EFFECTS
Moderator– Dr Panna Jain
Presented by – Dr Nitish Upadhyay
2. INDEX
I. Crystalloids
A. Introduction
B. Mechanism of action
C. Types of crystalloids
1. Ionic solution
i). Normal saline
ii). Dextrose saline
iii). Ringers lactate
iv). Isolyte-P
2. Non-ionic solution
i). 5% Dextrose
ii). 25% Dextrose
II. Colloids
A.Introduction
B. Types of colloids
1. Naturally occurring
i). Human albumin solution( 5% & 25%)
ii). Plasma protein fraction
iii). Fresh frozen plasma
iv). Immunoglobulin solution
2. Semisynthetic colloid
i). Dextran
ii). Gelatin
iii). Hydroxyethyl starch (HES)
3. CRYSTALLOIDS
INTRODUCTION –
• DEFINITION – crystalloids are solution of crystalline solids in water.
• GENERAL CHARACTERSTICS –
• Water & electrolytes similar to ECF e.g. ringer lactate( though w.r.t. Na+ → hypotonic)
• Nonionic solution ( not containing Na+) –e.g, dextrose 5% - dextrose gets metabolised → infused
water enters both intracellular space & extracellular space in proportion to their initial volumes
→ NONIONIC SOLUTION EXPANDS ALL THE COMPARTMENTS.
• Na cannot gain access to the intracellular space because of Na/K pump & nature of cell
membrane.
• If isotonic solution e.g. 0.9% saline → all sodium remains in extracellular space (isotonic solution
→ no exchange across cell membrnane.) → ISOTONIC IONIC SOLUTION EXPANDS
EXTRACELLULAR SPACE ONLY
4. • MECHANISM OF ACTION
• Crystalloids containing sodium in similar concentration to plasma eg 0.9% saline are rapidly
distributed throughout the extracellular space(ECS){intravascular & interstitial space}
• Ultimately only 25-30% of the volume administered remains intravascular. Hence approximately
3 times the volume needed to be given to expand the circulating volume
• Compared with 0.9% saline, RL provide small quantities of other electrolytes, which are
inadequate to meet daily maintenance requirements
CRYSTALLOIDS
6. NORMAL SALINE
I. Properties
i. 0.9 gm of NaCl in each 100 ml of water or 154 mmol/L of Na & Cl
ii. pH = 4 (acid load = 0.8 mmol/L)
II. Pharmacological Basis
I. Isotonic saline – slightly hypertonic : slightly lower pH(acidic) than plasma → rarely clinically
significant
II. Called NORMAL- isotonic & isosmotic with ECF ( & not in the chemical sense)
III. Provides major extracellular electrolytes - Na & Cl
IV. Corrects both fluid & electrolyte deficit
7. • INDICATIONS
1. Hypovolemic shock
• Ideal fluid to increase BP
• Fluid of choice when glycemic status is not known in trauma patients
2. Contains no buffer or other electrolytes – preferred to RL in
• Brain injury
• Hypochloraemic metabolic alkalosis
3. Hyponatremia
4. Patients with hyperkalemia (inc renal failure patients) – as it contains no K
5. Irrigation of washing of body fluids
6. Fluid challenge in prerenal acute renal failure(ARF)
7. Gastrointestinal losses e.g. gastric aspirate, paralytic ileus
8. Water & sodium depletion as in excessive perspiration, vomiting, diarrhoea, & excessive diuresis
9. Initial fluid therapy in diabetic ketoacidosis & hyponatremia
10. Can be given safely with blood
NORMAL SALINE
8. • CONTRAINDICATIONS
1. Patients with Na retention - preeclamptic patients, edema due to congestive cardiac failure
2. Pulmonary edema
3. Severe hypokalemia with dehydration
• ADVANATGES
• Easier for effective blood volume & blood pressures in emergencies
• DISADVANTAGES
1. Large doses or rapid infusion of large quantity → sodium accumulation & pulmonary edema
2. Chloride content > plasma (154 vs 103 mEq/L) → hyperchloremic metabolic acidosis
3. Febrile reaction (occasionally)
NORMAL SALINE
9. • PRECAUTIONS
1. When used in large volumes → mild hyperchloremia ( non-ionic gap metabolic acidosis )
2. Careful administration in extremes of ages
3. Restricted intake
• Impaired renal function
• Hypertension
• Peripheral & pulmonary edema
• Toxemia of pregnancy
• Cirrhosis of liver
NORMAL SALINE
10. DEXTROSE SALINE
• COMPOSITION
1L of fluid Dextrose Sodium Chloride
50gm 154mEq/L 154mEq/L
100 ml of fluid Dextrose Sodium chloride
5.0 gm 0.9gm
• PHARMACOLOGICAL BASIS
• Dextrose saline has advantages of both – 5% dextrose & 0.9% saline
• Dextrose – supplies energy
• Saline provides salts – major extracellular electrolytes along with fluid to correct dehydration
11. • INDICATIONS
1. Combined water & Na depletion – isotonic NaCl & 5% dextrose allows some of Na free water to
enter the cell which suffers most of dehydration . It will also correct salt depletion
2. Can be infused in dehydration with hypovolemic shock provided CORRECTION IS NOT NEEDED
RAPIDLY
• Faster infusion → osmotic diuresis (like 5% Dextrose → worsening dehydration & shock →
false impression of correction of shock due to improved urine output
3. Compatible with blood transfusion
4. FLUID OF CHOICE – corrects salt depletion , hypovolemia &also suppllies energy
I. Vomiting
II. Nasogastric aspiration – producing alkalosis with hypochloremia
DEXTROSE SALINE
13. RINGER’S LACTATE
• INTRODUCTION
• INTRODUCED BY “SIDNEY RINGER” in 1880 – designed to promote the contraction of isolated
frog’s heart
• 1930 AMERICAN PEDIATRICIAN – ALEX HARTMANN –proposed addition of Na-Lactate -
treatment of metabolic acidosis
• LACTATED RINGER’S SOLUTION – HARTMANN SOLUTION
• COMPOSITION
I. Potassium & calcium in concentrations - approximating free ionic concentration in plasma
II. Less sodium than isotonic saline
III. Addition of lactate (28mEq/L) → reduction in chloride → approximating free ionic concentration
in plasma
14. • COMPOSITION
RINGER’S LACTATE
1 L of fluid
supplies
sodium Chloride Potassium Calcium Bicarbonate(as
lactate)
131 mEq/L 111 mEq/L 5 mEq/L 4 mEq/L 29 mEq/L
100 ml fluid
contains
Sodium chloride Sodium lactate Potassium
chloride
Calcium chloride
600 mg 320 mg 40 mg 27 mg
• PHARMACOLOGICAL BASIS
1. Most physiological fluid – can be transfused rapidly in large maounts
2. High sodium concentration – rapidly expands intravascular volume like isotonic saline
15. • INDICATIONS
1. Replacement fluid in burns & postoperative patients
2. Can be safely used for initial treatment of diarrhoea induced dehydration in paediatric patients
– hypovolemia with hypokalemic metabolic acidosis induced by diarrhoea - effectively treated
3. Na-Lactate metabolised in liver → bicarbonate → correction in metabolic acidosis
4. Useful in surgical procedures – provides bicarbonate with all electrolytes
5. Corrects metabolic acidosis – provides dextrose free water with added advantage of supplying
potassium,
6. Can be used instead of isotonic saline during surgery or in initial management of injured
patients
RINGER’S LACTATE
16. • CONTRAINDICATIONS
1. Patients with VOMITING & NASOGASTRIC ASPIRATION {F.O.C DNS) – hypovolemia & metabolic
alkalosis – RL can worsen alkalosis ( bicarbonate)
2. Severe liver disease→ impaired lactate metabolism - RL can lead to acidosis
3. THIOPENTAL , ampicillin SHOULD NOT be mixed with RL since calcium in RL can bind with
above drugs & reduced bioavailability
• PRECAUTIONS
1. Calcium in RL → inactivation of anticoaugulant →Formation of clots when given with blood
transfusion
2. Should not be given in severe blood loss as a plasma substitute
3. Unsuitable for routine use as a sole intravenous fluid in post-operative period due to high
electrolyte content
RINGER’S LACTATE
17. ISOLYTE - P
• COMPOSITION
I Litre of fluid supplies 100 ml of fluid supplies
Dextrose 50gm Dextrose 5 gm
Sodium 23 mEq Sodium acetate 320 mgm
Chloride 20 mEq Potassium chloride 130 mgm
Potassium 20 mEq Dipotassium hydrogen
acetate
26 mgm
Magnesium 1.5 mEq
Phosphate 1.5 mEq Magnesium chloride 31 mgm
acetate 23 mEq
• PHARMACOLOGICAL BASIS
• Isolyte p was always used as maintenance fluid for children in the past -provides electrolytes, maintains pH,
supplies calories & replaces water deficit
• According to new APA guidelines on perioperative fluid management in children v1.1 September 2007 review
August 2010 , the maintenance fluid used during surgery should be isotonic, such as 0.9% Saline or RL
18. • INDICATIONS
• patients with diabetes insipidus will have excessive water loss or inability to concentrate urine
• CONTRAINDICATIONS
1. Isolyte P can aggravate hyponatremia (lowest concentration of sodium <20mEq/l)
2. Not the fluid of choice to correct intravascular volume (hypovolemic shock) & hypotension due to low Na
concentration
• PRECAUTIONS
• Isolyte P can cause hyperglycemia & osmotic diuresis even in children when given rapidly not safe in oliguric
children due to high K (20mEq/L)
ISOLYTE - P
19. 5% DEXTROSE
• PROPERITES
1. 5% dextrose in water solution is not an effective volume expander – functions as free water –
dextrose is metabolised → isososmotic – does not cause hemolysis
2. Most often used for prevention of hypoglycaemia in diabetic patients
3. May be used to correct hypernatremia
4. 5% dextrose – 50 grms dextrose per litre – 170 kcal per litre
I. 5 grams of dextrose in each 100 ml of water
II. Isotonic with plasma
III. Ph – 4.55
IV. Acid load 0.28mmol/l
V. 5% dextrose solution are suitable for diluting drugs (EXCEPT ACID LABILE DRUGS )
• PHARMACOLOGICAL BASIS
1. Iv administration – corrects dehydration & supplies energy
2. After dextrose metabolism – remaining water distributed in all compartments in proportion to
their initial volume
3. F.O.C – patients who need more water ; fewer electrolytes;
4. Ideal fluid for correction of intravascular dehydration
20. • SAFE RATE OF AMDINISTRATION
1. 0.5gm/kg body weight/hr - can be safely given without causing hypoglycaemia
2. Rapid transfusion – osmotic diuresis – dehydration
• METABOLISM
• Dextrose metabolised leaving free water
• Proportion contributing to lactate formation - 5% in normal patietns to 25%in critically ill patients
• Routine use abandoned in critically ill patients
5% DEXTROSE
21. • INDICATIONS
1. Management of hyperkalemia , during management of diabetic ketoacidosis – regimens with calcium,
bicarbonate & insulin
2. Replacement of insensible fluid loss – e.g. high grade fever
3. Prevention or treatment of ketosis in starvation, diarrhoea & vomiting
4. Replace water deficits with non significant loss of electrolytes
I. Average water requirement in adults – 1.5-2.5 litres daily - to be balanced with unavoidable losses (
skin & lungs) after providing sufficient water for urinary excretion
II. Water depletion occurs – when losses are not matched with comparable intake e.g. coma patients,
old age
III. Hyperthyroidism
5. Diabetes insipidus ; hypercalcemia – uncommon water losing renal states
6. Excessive use of electrolyte solution → hypernatremia – corrected by – 5% dextrose with frusemide –
promotes Na excretion
5% DEXTROSE
5% DEXTROSE
22. • CONTRAINDICATIONS
1. HYPOVOLEMIC SHOCK –
a) Produces expansion of interstitial & intravascular space with poor expansion of intravascular volume
b) Faster infusion - >0.5mg/kg/hr or >25gm/hr → osmotic diuresis
c) Osmotic diuresis → fluid loss by urine output in hypovolemia → false impression of correction
2. Neurosurgical procedures
• CONTRAINIDICATED
• Increases cerebral edema → increases damage during neurosurgery
3. Cerebral edema
a) Aggravates edema due to hypotonicity
b) Free water reduces serum osmolarity → increases brain water content
c) 65% decrease in colloidal osmotic pressure → no acute effect on cortical water content
d) 4%(13mOsm/Kg) decrease in plasma osmolarity → increase in brain water
4. Acute ischaemic stroke
a) Hyperglycemia – aggravates cerebral ischaemic brain damage – worsen the outcome of focal /global ischaemia :
dextrose metabolism enhances tissue acidosis in ischaemic areas
b) Hyperglycemia – reduction in adenosine levels(inhibits release of excitatory aminoacids)
5. Blood transfusion
a) Hypotonic – causes hemolysis
6. Uncontrolled diabetes & severe hyperglycemia
7. Hyponatremia & water intoxication
8. HYPERNATREMIA
1. RAPID INFUSION – corrects hypernatremia
2. SLOW INFUSION – causes hypernatremia
5% DEXTROSE
23. • ADVANTAGES
• Fluid of choice for - patients likely to retain Na & at risk of heart failure
• First 24 hrs after surgery – Na retention is common
• Adequate transfusion also protects liver from toxic substances
• DISADVANTAGES
• IV administration- local pain. Venous irritation, thrombophlebitis
• Prolonged administration – hypomagnesemia, hypophosphatemia & hypokalemia
• In critically ill patients – increased CO2 production, enhanced lactate levels, aggravation of ischaemic brain
injury
• PRECAUTIONS
• Addition of 5% dextrose to IV fluids – increases osmolarity
• 50 gm dextrose – 278 mOsm/L
• 5% dextrose + RL(278 mOsm/L) – 525 mOsm/L
• 5% dextrose + 0.9% saline( 310 mOsm/L) – 560 mOsm/L
• Impaired dextrose metabolism (critically ill ) → accumulation of glucose → undesirable osmotic force →
promotes cell dehydration
5% DEXTROSE
24. COLLOIDS
• INTRODUCTION
• DEFINITION : Colloids are large molecular weight( nominally Mw > 30,000) , homogenous, noncrystalline
substances that largely remain in intravascular compartment
• Important in CAPILLARY FLUID DYNAMICS – only constituents effective in exerting an osmotic force
across the capillaries {loses this property once capillary membranes are altered in diseased states}
• GENERAL CHARACTERSTICS
1. MOLECULAR WEIGHT
o Two molecular weights
i. Mw : weight average molecular weight – molecular weight measurements that depend on the
contributions of molecules according to their mass give weight average molecular weight →
determines viscosity
ii. Mn : number average molecular weight – simple arithmetic mean – total wt of all the polymer
molecules in a sample divided by no. of polymer molecules in a sample → determines oncotic &
osmotic pressures
2. Colloidal molecular size
o Determines dispersity
i. Monodisperse – e.g. Albumin Mw= Mn
ii. Polydisperse – e.g. FFP
o Gelatin lowest molecular weight; HES –highest molecular weight
25. COLLOIDS
• GENERAL CHARACTERSTICS
3. PLASMA VOLUME EXPANSION
i. Mw → Degree of volume expansion
ii. elimination of the colloid → Intravascular persistence
iii. Colloid osmotic pressure → potency
iv. Plasma volume expanders – increase the oncotic pressure in intravascular space → water moves
from interstitial space to intravascular space → increase in circulating volume → increase in
venous return → CO → SV → BP →urinary output & capillary perfusion → decrease in HR ,
peripheral resistance & blood viscosity
v. Generally administered in volume equal to lost plasma volume
vi. Duration of volume expansion variable among colloids – gelatin – shortest duration
4. Osmolality
• Almost all colloids solutions have normal osmolality
5. Colloid osmotic pressure
• oncocity → vascular expansion
• Proteins in plasma - responsible for COP
• COP can also be produced by large molecules present in colloidal solution e.g. Albumin,
Hetastarch, Dextran
i. COP opposes hydrostatic pressure. A colloid with large no. of small molecules – short duration of
action ( leak out of the circulation)
ii. Colloid with large no. of large molecules – longer duration of action (remain in circulation for
longer time
26. • GENERAL CHARACTERSTICS
6. Plasma half life
depends on Mw & elimination rate
7. Electrolyte content
• Sodium concentration is low in ‘salt poor albumin (25% albumin)
• In other commercially prepared colloids - Na concentration is similar to crystalloids
• Gelatin – urea linked - small( but not negligible ) K & Ca
- succinylated - negligible K & Ca
8. Acid –Base composition
Albumin & Gelatin – physiological pH
other solutions – acidic pH
COLLOIDS
27. • TYPES OF COLLOIDS
1. Naturally occurring plasma derivative
I. Human Albumin Solutions
a) 5% Albumin
b) 25% Albumin
II. Plasma protein fraction (PPF)
III. Fresh Frozen Plasma
IV. Immunoglobulin solution
1. Semisynthetic colloids
I. Dextran
a) 10% Dextran 40 in 0.9% saline
b) 6% Dextran 40 in 5% Dextrose
c) 6% Dextran 70 in 5% Dextrose
II. Gelatin
a) Urea cross linked gelatins
• Polygeline ‘Haemaccel’; Hoechst
b) Succinylated or modified fluid Gelatins (MFGs)
• Gelofusine
• Plasmagel
• Plasmion
c) Oxypolygelatins
• Gelifundol
COLLOIDS
28. • TYPES OF COLLOIDS
2. Semisynthetic colloids
III. Hydroxyethyl starch
a) 1st Generation
• Hetastarch – 450/0.7 – Hestar – 450 (0.9% saline)
• Hetastarch – 600/0.7 – 6% Hespan or Hetaspan ( 0.9% saline)
• Hetastarch – 450/0.7 – 6% Hextend (Ringer’s Lactate)
b) 2nd Generation
• Pentastarch
• 3% HES – 200/0.5 - Steril
• 6% HES – 200/0.7 - Steril
• 10% HES – 200/0.7 - Steril
c) 3rd Generation
• Tetrastarch
• 6% HES 130/0.4 – voluven in normal saline
• 6% hes 130/0.4 – volulyte in ana isotonic electrolyte solution
COLLOIDS
29. COLLOIDS
• INDICATIONS OF COLLOIDS
1. Emergency treatment of shock especially due to loss of plasma
2. Large protein losses- acute management of burns
3. Clinical situations of hypoalbuminemia
i. Following paracentesis
ii. Liver cirrhosis (ECAD – extracorporeal albumin dialysis)
iii. After liver transplantation
iv. Fluid resuscitation - prior to blood availability for transfusion (haemorrhagic shock)
v. In conjunction with crystalloids – if fluid load exceeds 3-4 L prior to transfusion
vi. Fluid boluses in critically ill patients e.g. ICU, pulmonary edema, CCF, renal conditions etc
30. HUMAN ALBUMIN
• General properties
1. Principle natural colloid – 50-60% of all plasma proteins
2. 80% of normal oncotic pressure
3. Single polypeptide chain – 585 amino acids – Mw – 69000 Dalton
4. Ellipsoid molecule, nonviscous, flexible in nature – preservation of structure in RBC
• Albumin Synthesis
1. Influenced by
a) Nutritional status
b) Hormonal environment e.g. GH, ACTH, Insulin, Testosterone
2. 30% synthesized in liver – can compensate for 2-5 times loss of albumin
3. Inflammatory cytokines ( TNF, IL-6 ) decreases albumin synthesis
• Shelf life & storage Temperature(ºc) Shelf life
20-25 3 years
2-8 5 years
After opening vial 4 HOURS
31. TYPES OF ALBUMIN
• All commercially available preparation – heat treated preparation - 60ºc for 10hrs → inactivate hepatitis viruses & HIV
I. 5% albumin solution ( 50gm/L or 5mg/100ml)
a. No preservative; clear to yellow or green, viscous liquid
b. Composition
a. Degree & duration of expansion - depends on initial blood volume
• IV administration- volume expansion is equal to the volume infused
• Diminished blood volume – effect of infused albumin lasts for many hours
• Normal blood volume – effect lasts for shorter time
HUMAN ALBUMIN
Component Quantity ( 1000ml)
Protein of which >96% is human albumin 50gm
Sodium 130-160mEq/L
Potassium <2 mmol/L
N-acetyl – DL – tryptophan 0.064-0.096 mmol/gm protein
Caprylic acid 0.064-0.096 mmol/gm protein
Water for injections 1000ml
32. I. 5% albumin (contd..)
• 5% albumin – isotonic - 80% volume expansion – lasts 12-18 hrs
• 25% albumin - hyperoncotic - 200-400% volume expansion – within 30min lasts for 16-24hrs
• COP – 20 mm Hg
• Total body albumin in 70 kg man – 350gm – t1/2 →13-19 days – turnover 15gm per day
• Primarily used in treatment of shock a/w surgery; haemorrhage; trauma; burns; renal failure; & cardiovascular collapse
II. 25% albumin
• 96% albumin + 4% globulin → diluted to 5% solution before infusion
• Contains purified albumin 5 times the normal concentration → potential to expand 4-5 times the volume
• COP – 70 mm Hg
• It is selected when the current plasma volume is diminished but “blood pressure is acceptable” & “total ECF compartment
is expanded”
III. Plasma protein fraction
• Available as 5% solution in electrolytes – contains 83% albumin + 17% alpha & beta globulins
HUMAN ALBUMIN
33. • Functions of albumin in health
1. COP – exerts colloidal osmotic & oncotic effect at the level of capillaries
2. Coagulation
• Decreases platelet aggregation
• Heparin like activity
• Formation of normal anion gap
3. Transport of compounds
• Calcium ; magnesium
• Bilirubin, fatty acids, vitamin d, thyroxin
• Drugs – warfarin ; phenytoin – harmful effects
- Ceftriaxone – benificial effects
4. Metabolism
• After synthesis – not stored but released in blood – 42% remains in intravascular blood
• In health synthesis matches metabolism
HUMAN ALBUMIN
34. • ALBUMIN IN CRITICALLY ILL PATIENTS
1. Prognostic marker
• In critically ill aptients survivors have a higher serum albumin concentration than non-survivors
2. Value of albumin replacement
• Unclear
• Children – improvement of absorption of food
• Neonates – treatment of hypotension metabolic acidosis, & promote diuresis
3. Ineffective in following conditions
• Septic shock
➢ Release of inflammatory mediators – increase in leakiness of vascular endothelium – administration of albumin →
adds to interstitial edema
• Hypoalbuminemia – unknown
• Increased catabolism – underling cause not treated
HUMAN ALBUMIN
35. • INDICATIONS FOR THE INFUSION OF ALBUMIN
1. Hypovolemic shock - emergency treatment
• Isooncotic - expands plasna equal to amount infused
• Volume deficit - 5% best
• Oncotic deficit - 25% better ( with adequate crystalloids)
2. Burn therapy
• 1st 24 hrs crystalloids(large volume)
• Restore ECF
• Post 24hrs albumin --> maintain plasma Oncotic pressure (target --> 5.2gm/100ml)
3. Acute liver failure
- double purpose- COP of plasma as well as binding excess plasma bilirubin
4. Sequestration of protein rich fluids
• In acute peritonitis, pancreatitis, mediastinitis, & extensive cellulitis -5% preferable
5. Cardiopulmonary bypass
• Modern pump- small priming volume required --> preoperative dilution with albumin is preferred
• Target - hematocrit -20%
• Plasma albumin - 2.5gm/100ml
HUMAN ALBUMIN
36. • INDICATIONS (CONTD..)
6. Others
• Transport protein - in HDN (severe jaundice)
• Paracentesis for asicitc fluid- maintenance of cardiovascular function
• Immunoglobulin deficiencies
• Plasma cholinesterase deficiencies
• Therapeutic plasmapharesis- exchange fluid to replace removed plasma
• CONTRAINDICATIONS
1. Hypersensitivity
2. Chronic nephrosis- infused albumin promptly excreted by kidneys
3. Hypoproteinaemic state- chronic cirrhosis, malabsorption, pancreatic insufficiency, stabilized chronic anaemia - use of
albumin as source of protein is not justified
4. CCF, Renal insufficiency, srabilized chronic anaemia
HUMAN ALBUMIN
37. • SIDE EFFECTS
1. Nausea, vomiting, allergic reaction includin anaphylactic shock
2. Circulatory overload
3. Febrile reaction
4. Hypotension - due to vasoactive substances
• PRECAUTIONS & SAFETY
1. Cloudy or have deposits in solutions - DO NOT USE
2. Unused portion - DISCARD
3. MUST NOT BE DILUTED WITH WATER - May cause hemolysis
4. Electrolytes status should be monitored (20-25 % albumin -low in electrolytes)
5. PLASMA VOLUME EXPANSION IS AT THE COST OF INTERSTITIAL FLUID SHIFT - 20% albumin should be used with proper
amount of crystalloids
6. If large volumes to be transfused - control for hematocrit & coagulation necessary- may require replacement with other blood
constituents
7. Circulatory overload
HUMAN ALBUMIN
38. • ADVANTAGES
1. Natural colloid- lesser side effects
2. Degree of volume expansion- 25% albumin maximum among colloids
5% albumin = hetastarch > gelatins,
dextrans
3. Others -
• Principal binding protein
• Antioxidant
• Scavenging action
• Formation of normal anion gap
• DISADVANTAGES
1. cost
2. Volume overload
HUMAN ALBUMIN
39. • DOSAGE & ADMINISTRATION
1. Adjusted according to patient's requirement - depends on age / severity of trauma / continuing fluid & protein losses
2. Adequate hemodynamic monitoring
• Serum Oncotic level < 20mmHg ( total protein concentration -5.2gm/ 100ml--> treated with 25 % albumin
A. Hemorrhagic shock
• Volume infused - related to estimated volume deficit & speed of administration
• Neonates & infants - 5 % albumin can be given in large amounts
• Recommended dose-10-20 ml/kg equivalent to 0.5-1gm albumin /kg body weight
B. Burns
• After 24 hrs - Target plasma albumin concentration - 2.5 ± 5.2gm / 100ml with plasma Oncotic pressure of 20mm Hg -
best achieved by 25 % albumin
C. after liver transplantation
• 100 -400 ml of 25% albumin daily
• Children 1.5ml/kg in 24 hr
HUMAN ALBUMIN
AMOUNT OF ALBUMIN TO BE TRANSFUSED
ADULTS VOLUME RATE OF INFUSION
5% SOLUTION 500ml 1-2 ml/min
25% SOLUTION 100ml 1 ml/min
40. • DRUG INTERACTIONS
• compatible with whole blood & packed red blood cells
• compatible with standard carbohydrate & electrolyte solutions
• SHOULD NOT be used with protein hydrolysates, amino acid solutions, not that containing alcohol
HUMAN ALBUMIN
41. DEXTRAN
• GENERAL PROPERTIES
• Highly branched polysaccharide molecules
• High molecular weight
• Use as artificial colloid
• Dextran solutions - water soluble dextrose polymers synthesized by bacteria from sucrose
• Degraded enzymatically to dextrose
• Can be stored for many years at room temperature in powdered form or as a solution
• TYPES OF DEXTRAN
TYPE NAME Mw INTRAVASCUALR LIFE
Dextran 40 (10% polysaccharide) LOMODEX 40,000 4-6 hrs
Dextran 70 (6% polysaccharide) MACRODEX 70,000 6-8 hrs
42. • CLINICAL EFFECTS & ADVANTAGES
1. Plasma volume expanders
• Efficacy equal to or superior to albumin
• Dextran 40/70 higher volume expansion than HES
• Duration - 6-12 hrs
• Hyperoncotic to plasma -COP :40mmHg
• Dose needs to be reduced in bleeding & perioperative patients to 1000ml-1500 ml per 24hrs - effect on clotting
• Dextran 40 - higher oncotic effect per gram --> larger increase in plasma volume than Dextran 70; effect lasts
for only few hrs
• 500ml Dextran 40 --> 750ml intravascular volume expansion in 1hr --> used in vascular surgeries to prevent
thrombosis (rarely as volume expander)
• Dextran 70 - volume replacement preferred - prolonged action ; maintain intravascular volume over a period of
time
• Dextran -100-150% increase in intravascular volume
• Dose : 1-2gm/kg
DEXTRAN
43. 2. Thromboprophylactic effects
• Proved Thromboprophylactic effects --> hemodilution--> prevents cell aggregation(particularly in
sensitive region of terminal vascular bed, past the capillaries on the venous side)
• Antithrombotic effect is due to
i. Augmentation of microcirculation
ii. Inhibit erythrocytic aggregation & rouleax formation --> reverse & prevent erythrocytic
sludging
iii. Depresses factor VIII activity --> increases susceptibility of thrombi to fibrinolysis
• METABOLISM AND EXCRETION
• Primarily renal - remain unchanged
i. Depends on molecular size - smaller (14000-18000Da) excreted in 15 min ; large molecules
stay in circulation for several days
ii. 40% of dextran -40 & 70% of dextran-70 remain in circulation at12 hrs - unexcreted part
absorbed in RES
iii. RES --> Metabolised in liver to water & carbon dioxide
DEXTRAN
44. • COMPLICATIONS & DISADVANTAGES WITH DEXTRAN ADMINISTRATION
1. Anaphylactic reaction
• More reactions than gelatin or starches
• 1 in every 3300 administrations.
• Dextran reactive antibodies --> release of vasoactive mediators
• Can be reduced by pretreatment with hapten
• Typically occur early in the infusion period in patients with no previous exposure to dextran even with
doses as small as 0.5 gm --> CLOSELY MONITOR patients with no previous exposure ; Especially IN THE
FIRST FEW MINUTES
• Discontinue infusion at first sign if allergic reaction
• Immediate medical intervention(- parenteral epinephrine, antihistamines, supportive therapy)keep
resuscitative measures readily available during dextran use
• Incidence decreased - 0.032-0.07%
DEXTRAN
45. • COMPLICATIONS & DISADVANTAGES WITH DEXTRAN ADMINISTRATION(contd..)
2. Interference with blood cross matching
• Coat platelets, coagulation factors, RBCs--> interfere with ability to cross match
• Obtain blood specimen before infusion
3. Coagulation abnormalities
• A/w significant bleeding complications in dose dependent manner
• Inhibit platelet adhesiveness (dose> 20ml/kg/ 24 hrs ) ,reduced factor VIII activation, promotes fibrinolysis, decreases
endothelial coating
• Rare cases of noncardiogenic pulmonary oedema due to dextran - direct toxic effect on pulmonary capillaries
4. Precipitation of ARF
• Dextran increases viscosity & specific gravity of urine (especially in pt with decreased urine flow)
• Low specific gravity of urine during dextran therapy may indicate a failure of renal dextran clearance- advisable to
discontinue dextran
• Mechanism
• Hyperoncotic state --> reduced filtration pressure --> accumulation of dextran molecules--> tubular plugging --> renal
failure --> use limited in hypovolemia
DEXTRAN
46. • COMPLICATIONS & DISADVANTAGES WITH DEXTRAN ADMINISTRATION(contd..)
• Precautions to avoid renal failure
1. Assess adequate hydration
2. Decreased urine output is secondary to shock - dextran 40 can be used
3. Discontinue if oliguria or anuria occurs
5. Overloading precipitates CCF
- especially when administered in sodium chloride.
• CONTRAINDICATIONS
1. Known hypersensitivity
2. marked cardiac decompensation
3. Renal disease with severe oliguria or anuria
4. Marked haemostatic defects (e.g. thrombocytopenia, hypofibrinogenia, heparin/warfarin induced)
5. Extreme dehydration ( controversial)
DEXTRAN
47. • SPECIAL PRECAUTIONS
1. Circulatory and/or volume overload
• Monitor CVP
• Immediate discontinuation - rise in CVP (any signs of circulatory overload)
2. Renal effects
• Crystalloids should be transfused same quantity
DO NOT GIVE
• if urine output <1500ml/day or blood urea > 60mg%
• If urine output decreases
• Specific gravity > 1.045
3. Dextran > 1.5gm/kg/day --> blood clotting hindered
4. Hepatic effects
• Abnormal LFT
DEXTRAN
49. • CLINICAL USES
1. Therapy for impaired circulation in terminal vascular bed during periods of prolonged shock,
maintaining vascular graft patency, cerebrovascular insufficiency, myocardia ischaemia, &
hyperviscosity syndrome
2. To improve microcirculation in microsurgical implantations
3. Plastic surgery, especially flap surgery – maintains & assist in preservance of pedicle vascular integrity
4. Thromboembolic disease – treatment & prevention – in patients having peripheral vascular disease
5. Endarterectomy , stent grafting & other vascular procedures – prevention of excessive platelet
activation & release of microemboli
6. As a plasma substitute for priming in extracorporeal circulation
DEXTRAN 40
50. • REGIMEN FOR SHOCK
• Depends on patients need
• Adult in shock usually required 500 ml of rapid iv infusion
• Day 1 : 20 ml/kg for 24 hrs
• Upto day 5 : 10ml/kg for 24 hrs
• REGIMEN FOR PREVENTION OF THROMBOEMBOLISM
• Day 1 : 500-1000 ml over 4-6 hrs
• Day 2 : 500 ml over 4-6 hrs
• Day 3 : 500 ml over 4-6 hrs on alternate day upto 20 days
• REGIMEN FOR SURGICAL PROPYLAXIS
• 500 ml given preoperatively & postoperatively daily for 4 days
DEXTRAN 40
51. • PHARMACOLOGICAL BASIS
• Longer half life than Dextran 40
• 6% polysaccharide solution in 5% Dextrose (but not in saline)
• Total dose SHOULD NOT exceed 20 ml/kg in first 24hrs & 10 ml/kg on subsequent days
1. Main indication – volume replacement for blood loss & shock
2. Thromboprophylaxis – not as effective as Dextran 40
• D.O.A – 6-8 hrs
• METABOLISM
tends to be retained in body especially in liver & RES
DEXTRAN 70
Metabolism of Dextran 40 & Dextran 70
Dextran 40 Dextran 70
Short plasma half-life
40-70% excreted by kidney within 24 hrs Not excreted from the body
Most of remainder is metabolised Slowly oxidised over the periods of weeks
52. Dose of dextran 70 & dextran 40 in various clinical condition
Clinical condition Infants Children Adults
Dextran 70
Shock Rapid infusion 500ml
Total dose not to exceed
20ml/kg
10ml/kg
Upto 5 days
Dextran 40
Shock 0.5gm/kg
5ml/kg
1gm/kg
10ml/kg
2gm/kg
20ml/kg
1gm/kg
10ml/kg daily for
upto 5 days
Surgical prophylaxis of
thromboembolism
0.5gm/kg 1gm/kg 500-1000ml
50-100gm
10ml/kg
Day 1
500ml
50gm
Daily for an
additional 2-
3days
500ml
50gm every 2-3
days for upto 2
weeks
According to the risk
of thromboembolic
complications
5ml/kg 10ml/kg
Thromboembolism 500-1000ml over 4-6 hr day 1 500 over 4-6 hr
day 2
500 ml over 4-6 hr
upto 20 days on
alternate day
53. GELATIN SOLUTIONS
• DEFINITION
• Gelatin is the name given to the proteins formed when the connective tissue if animals are boiled
• Have the property of dissolving in hot water & forming a jelly when cooled
• Large molecular weight protein – formed from hydrolysis of collagen
• Target – moderate molecular weight (for oncotic pressure) ,low gel melting point(difficult to infuse a
jelly)
1. Group of molecules developed to fill the gap between crystalloids & blood products
2. Easy to store , relatively short acting, do not affect coagulation, safe to use
3. Not considered as significant plasma expander
54. • TYPES OF GELATIN IN COMMON USE
• Called as NEW GENERATION GELATIN
1. urea cross-linked gelatins
• Polygeine(Hemaccel, Hoechst)
• Production –cattle bone →action of alkali → action of boiling water(thermal degradation) → Polypeptide
(Mw 12000-15000) + hexamethyldiisocynate (urea cross linking)
• Final compound Mw ranges from 5000-50000
2. Succinylated or modified fluid gelatins (MEG)
• Gelofuscine , Plasmagel, Plasmion
• Succinylation →negative charge (supposedly spreads the molecule)
3. Oxypolygelatins
• Gelifundol
GELATIN SOLUTIONS
55. • PROPERTIES
• Polygeline -3.5% solution of degraded gelatin polypeptides cross linked via urea bridges with
electrolytes (Na+ 145, K+ 5.1 Ca++ 6.25 & Cl- 145mmol/L).
• Sterile, pyogen free, with no preservatives
• Recommended shelf life – 3 years (<30ºC)
• Succinylated gelatin – 4% gelatin in ionic solution supplied in 1000/500ml infusion bag – does not
contain Ca & K
• PHARMACOKINETICS
• Functions as volume replacement for distinctly SHORTER PERIOD OF TIME (approx. 2-3 hrs) because of
their low average Mw
• CLINICAL PHARMACOLOGY
• Leads to 70-80% volume expansion
• Shorter duration
• Fibrinogen function impaired after gelatin infusion
GELATIN SOLUTIONS
56. • METABOLISM & EXCRETION
• Rapidly excreted through kidney in unchanged form
• Infusion – 2.5 hrs peak plasma concentration – half
• No effect on renal impairment
• Readily excreted by glomerular filtration as they are small sized molecules – patients with ESRD can
still receive gelatins
• Not stored in RES
GELATIN SOLUTIONS
57. • ADVANTAGES OF GELATINS
1. No limit of infusion
• No upper limit
• No specific dosage limitations
• EXCEPT NECESSARY TO MAINTAIN CERTAIN MINIMUM Hb & A HEMATOCRIT > 25%
2. Cost effectiveness
• Cheaper & more readily available
3. No risk of infection
4. No effect of renal impairment
5. No effect on coagulation
6. Other advantages
• Long shelf life
• No refrigeration
• No interference with blood group cross matching
GELATIN SOLUTIONS
58. • DISADVANTAGES
1. Anaphylactoid reaction
• Higher incidence as compared to natural colloid albumin
2. Circulatory disturbances
• In patients with ascites undergoing large volume paracentesis
• Increase plasma renin activity
• Increase aldosterone
3. Overhydration
• VOLUME REPLACERS AS OPPOSED TO VOLUME EXPANDERS
• Rapidly migrate out of the intravascular space – needs more volume to achieve volume expansion
effect – raises the issue & possibility of overhydratiob
4. Higher cost
5. Theoretical risk of transmission of contagion form bovine source
GELATIN SOLUTIONS
59. • INDICATIONS
1. Prophylactic use in major surgery – to reduce total volume of replacement
2. Volume preloading prior to regional anaesthesia
3. Stabilization of the circulatory system during anaesthesia
a) Amount of gelatin infusion depends on
• Amount of intravascular fluid lost
• Speed with which it is lost
• Time elapsed since the first sign of shock
• Patients individual need
b) Rate of infusion depends on
• Arterial BP/Pulse rate
• Urinary output/CVP/ electrolyte
GELATIN SOLUTIONS
60. • INDICATIONS
4) Plasma volume substitutes
• First 20-30 ml should be infused slowly – watch for any adverse reactions
5) Hypovolemia
• Any types of hypovolemia – gelatin can be used
6) Oligaemic shock
7) Endotoxic shock, anaphylactic shock – can be given safely
8) Plasma exchange
• Decrease the initial hypotensive response during plasma exchange
9) Acute normovolemic hemodilution
10) Extracorporeal circulation
• Extracorporeal cardiopulmonary bypass
• May be used for priming the heart lung machine , the artificial kidney & hemodilution
11) Carrier for substances
GELATIN SOLUTIONS
61. • UNDESIRABLE SIDE EFFECTS
1) Anaphylactic & anaphylactoid reactions
• Highest incidence of reactions
• Cross reaction can occur
• Can occur on the first clinical use without previous exposure
• If present – infusion must be stopped immediately & treatment for anaphylactic reaction
2) Volume overload
• In patients with CCF or severe renal impairment – main risk is volume overload
3) Effects on coagulation
• Mixed data
• Polygeline – contains calcium → activates clotting cascade when mixed with citrated blood or FFP
4) Proteinuria
• Specific gravity may increase
• Significant proteinuria has been reported
5) Circulatory disturbance
GELATIN SOLUTIONS
62. HAEMACCEL
• PROPERTIES
1. Colloidal plasma substitute – polymer of degraded gelatin (35gm) with electrolytes
2. Mw – 30000
3. pH – 7.1
4. Contains calcium – can lead to increase in calcium levels following large volume resuscitator
5. Sterile, pyogen free, no preservatives
• METABOLISM & EXCRETION
• Low molecular portion – renal elimination immediately sets in
• Remaining part – proteolysis by endogenous proteases - prevents accumulation
• MODES OF ADMINISTRATION
• Ready for use solution
• In general should not exceed 125 drops per minute or 500ml/hr
• In emergencies – rapid infusion → 500ml in 5 -15 min
• Not to be mixed with citrated blood
63. • PRECAUTIONS
1. No preservatives- ensure clear solution before infusion
2. Contains large amount of calcium- clotting in citrated blood ( can be given with heparinized blood)
3. In fully digitalised patients- existing calcium ions may enhance the effect
4. Patients with allergic response risk or history of histamine repsonse- infusion after taking prophylactic
measures
• SIDE EFFECTS
• Potentially fatal histamine induced reactions
• Facial flushing to true anaphylactic reactions
• If reactions
• Mild: antihistaminics
• Severe : catecholamines + high dose corticosteroids+ volume replacement + oxygen
• Rare cases of air embolism- When transfused under high pressure
HAEMACCEL
64. • CONTRAINDICATIONS
• Existing severe allergic reactions
• Recommended dosage
1. Adults : in loss of blood and Plasma
• Shock prophylaxis : 500-1500ml can be given
• Volume deficiency shock: maximum 2000 ml
• In emergencies : volume as required
2. Children:
• Volume deficiency & emergencies : as required
" in the case of newborns, infants, children, geriatric patients - human albumin or preserved serum
should be used where possible in place of the synthetic colloid, in consideration of inadequate protein
reserve & loss of function of proteins ( geriatric cases)”
HAEMACCEL
65. GELOFUSINE
• PROPERTIES
• Mw - 35000
• pH - 5.8
• Similar to haemaccel BUT LESS CALCIUM
• low chloride - helpful in patients with hyperchloraemic acidosis
• Compatible with blood products ( less calcium)
• UNIQUE BENIFITS
• 100% Volume expansion
• Does not dehydrate the interstitial space
• Does not interfere with coagulation system
• has a very high dosage ceiling
• Does not interfere with BGCM
• Has no cumulative effect
• Many liters can be given provided patient has normal renal function
• INDICATIONS : SAME AS HAEMACCEL
66. HYDROXYETHYL STARCH
• GENERAL PHAMACOLOGICAL PROPERTIES OF HES
1. Concentration
HES Solutions are
3% -Hypooncotic
6% -Isooncotic
10% -Hyperoncotic
2. Molecular weight
MOLECULAR WEIGHT TYPES OF HES
High 450-670 kDa Hetastarch
Medium 130-200 kDa Hexastarch
Pentastarch
Tetrastarch
low 70 kDa
67. • GENERAL PHAMACOLOGICAL PROPERTIES OF HES
2. Molecular weight (contd..)
• High molecular weight (HES-450) & a degree of hydroxyethylation (0.7) delays splitting & elimination- longer stay in
intravascular space - volume effect is comparable to dextran-70 or plasma protein solutions
• Polydisperse system
• Small molecules below renal threshold (45-60kDa) are rapidly excreted
• Larger molecules are retained for variable times depending on size & ease of break down
• Large molecules -alpha amylase--> smaller molecules - excreted by kidneys
• Minor portion transiently stored in tissues - excreted in urine by redistribution
• Mw determines
• Water binding capacity--> volume expansion
• Cumulative effects with repeated or large doses
• High risk of side effects lie coagulopathy
• Lesser the molecular weight & degree of substitution - safer the molecule in terms of accumulation & effects on
coagulation
HYDROXYETHYL STARCH
INVIVO Mw STAY IN INTRAVSCULAR SPACE
Hetastarch HES 450/0.7 250kDa after 24 hrs
Pentastarch HES 200/0.5 120-140 kDa after 6 hrs
Tetrastarch HES 130/0.4 65-70 kDa after 30 minutes
68. • GENERAL PHAMACOLOGICAL PROPERTIES OF HES
3. Molar substitution (MS)
synthesized from Amylopectin(hydrolyzing corn/potato)- highly branched
starch hydroxyethyl residues HES
HYDROXYETHYL STARCH
69. • GENERAL PHARMACOLOGICAL PROPERTIES OF HES
3. Molar substitution (MS) (contd..)
• Pharmacokinetic parameters determined by molar substitution & the substitution pattern
1. Molar substitution is defined as the number of hydroxyethyl residues per dextrose subunit of the
starch molecule I.e. the modification of the original substance by the addition of hydroxyethyl groups
- increases the solubility in water
• High molar substitution -0.62-0.75
• Medium molar substitution- 0.5
• Low molar substitution -<0.4
2. Unsubstituted anhydroglucose -more prone to enzymatic degradation --> thus hydroxyethylation
slows down enzymatic breakdown & prolongs intravascular retention time
HYDROXYETHYL STARCH
GENERATION PRODUCT Mw(kDa) MOLAR SUBSTITUTION C2/C6 RATIO
1st generation Hetastarch 600 0.7 7 out of 10 dextrose units are hydroxyethylated 5:1
Hexastarch 200 0.62 6.2 out of 10 dextrose units are hydroxyethylated 9:1
2nd generation Pentastarch 200 0.5 5 out of 10 dextrose units are hydroxyethylated 5:1
3rd generation Tetrastarch 130 0.4 4 out of 10 dextrose units are hydroxyethylated 9:1
70. • GENERAL PHARMACOLOGICAL PROPERTIES OF HES
4. C2/C6 substitution pattern
• To make Amylopectin molecule more stable, dextrose residues are substituted with hydroxyethyl groups
at 3 positions (C-2,3,6)
• Predominance towards C2/C6 carbon atoms
• C2/ C6 ratio refers to the site where substitution by HES has occurred on the initial dextrose molecule.
• Can be low (<0.8) or high (> 0.8) depending on degree of substitution
• High C2/ C6 ratio indicates a decrease in the hydrolysis of HES by amylase - synergistic to high mlar
substitution
• Hydroxyethyl group at C2 inhibits access of amylase more than those at C6 position
• C2>C6> C3
• Higher the C2/ C6 ratio greater the difficulty in hydrolyzing HES by amylase --> longer the half life --> more
persistence in blood
•
HYDROXYETHYL STARCH
71. • DEGREE OF VOLUME EXPANSION
• Increase in COP - equivalent to albumin
• 100% volume expansion > gelatins
• NOMENCLATURE
• METABOLISM OF HES
• Steadily reduced over time by enzymatic cleavage
• Higher Mw & more extensive degree of substitution - slower elimination
i. Smaller - excreted immediately by kidneys
ii. larger molecules - first converted to smaller - then excreted
iii. Medium molecules - excreted in bile & faeces
• 30% in RES- mostly liver and spleen
HYDROXYETHYL STARCH
72. • DISADVANTAGES
• More with first & second generation HES
1. Coagulation
• HES molecule interacts with platelet & coagulation cascade
• Impairment of plasma clotting & factor VIII activity same as dextran
• Antithrombotic effect not established
A. HES administration is associated with
• Factor VIII reduction - due to dilution effect - prolongation of apTT - increasing bleeding complications
• VWF - activity reduced
• Impairment of platelet aggregation
B. Fibrinogen & VWF binding - required in normal platelet aggregation & endothelial adherence -interfered by
HES
HYDROXYETHYL STARCH
73. • DISADVANTAGES
C. Mw & degree of substitution - influence coagulation
• High molar substituted HES - considerable derangement effects on blood clotting , platelet function&
subsequently increased postoperative bleeding
• Least effects with rapid degrade HES- tetrastarch ( even with high dose 70ml/kg)
D. Alter coagulation in dose dependent manner(more effect with higher dose and more hemodilution)
E. Multiple studies data indicates that HES solutions ( with the exception of Voluven (6% HES130/0.4),
attenuates the availability of platelet GPIIb/IIIa receptors either by direct inhibition or nonspecific coating.
• Clot strength & clot formation is affected --> direct movement of the Hetastarch molecules into fibrin clot ,
thereby increasing the PT & Partial thromboplastin time.
.
HYDROXYETHYL STARCH
74. • DISADVANTAGES
2. Accumulation
• High molecular weight- greater degree of accumulation in interstitial space & RES.
• Main clinical manifestation - pruritus ( related to molar substitute& cumulative infused dose) resistant to
treatment by glucocorticoids , antihistaminics, acetaminophen, neuroleptic drugs.
3. Effects on renal function
• SOAP STUDY (sepsis occurrence in acutely ill patients) - not an independent risk factor for adverse effects on
renal function
• Effects are more prominent with high degree of substitution of HES , with high doses & least with tetrastarch
• High Mw HES - osmotic nephrosis
• Mechanism of renal dysfunction- repeated infusions--> hyperviscosity--> renal dysfunction in dehydrated
patients
• Patients with reduced kidney function ( creat> 2.5mg/100ml) HES SHOULD BE USED CAUTIOUSLY
• Patients at risk of developing kidney dysfunction- HES SHOULD NOT BE USED
HYDROXYETHYL STARCH
75. • DISADVANTAGES
4. Effects on cardiovascular system
• 6% HES --> Increased CVP, Pulmonary capillary wedge pressure, CO, & Ventricular stroke volume ( equivalent
to 5% albumin)
5. Effects on plasma bilirubin
• Waxy maize HES -not associated with liver dysfunction or any rise in bilirubin
• Potato derived starch- impairs excretion of bile --> causes increased bilirubin from fragmented erythrocyte
• POTATO DERIVED HES130/4.2 ARE THE ONLY TETRASTARCH TO BR ABSOLUTELY CONTRAINDICATED IN
PATIENTS WITH SEVERE HEPATIC IMPAIRMENT.
6.ANAPHYLACTIC REACTION
• Higher incidence than other synthetic colloids as well as albumin
• Hetastarch is not antigenic
HYDROXYETHYL STARCH
76. • DISADVANTAGES
8. Miscellaneous
• SPECIAL PRECAUTIONS
• Pancreatitis patient - compromise the interpretation of serum amylase values
• Elevated for first few days ( 2-3 times)--> return to normal at 5-7 days after therapy
• Serum lipase remain normal-distinguishing feature from early pancreatitis
HYDROXYETHYL STARCH
HYDROXYETHYL STARCH
SYSTEM ORGAN CLASS ADVERSE DRUG REACTION
Blood & lymphatic system Coagulation disorders
Immune system Anaphylactoid reactions
Skin & subcutaneous tissue Pruritus
investigations Increase in serum amylase
Decrease in haematocrit
Decrease in plasma proteins
77. • CLINICAL USES
1. Stabilization of systemic hemodynamic circulation
• Medium acting HES (130/0.4) appear to be suitable for volume deficit restoration - beneficial the hemodynamic
effects, fewer side effects
2. In infants & toddlers during surgery
• HES 6% 70/0.5 more effective than RL for plasma expansion
3. Treatment of increased ICP in neurosurgery
• Hypertonic saline in starch (7.2% saline/HES 200/0.5) more effective than15% mannitol in treatment of
increased ICP.
• Dose : 1.4ml/kg - effective & safe
4. Endotoxemia
• improve microcirculation due to anti-inflammatory properties
HYDROXYETHYL STARCH
78. • ADVANTAGES
1. Cost effectiveness
• Less expensive than albumin
2. Maximum allowable volume
• Medium molecular weight HES (130KDa) with medium degree of substitution (0.4) is 50ml/kg -
greater than other synthetic colloids like dextrans
HYDROXYETHYL STARCH
79. FIRST GENERATION HES - HETASTARCH - HES 450/0.7
• Pharmacodynamics
1. Average molecular weight of starch molecules is equivalent to that of albumin
2. 80% of polymers - Mw range from 10000-2million Daltons
3. COP-30mm Hg > 5% albumin (20mmHg)
4. Volume expansion 30% greater than infused volume
5. pH -5.5 & osmolality is about 310mOsm/L
6. Plasma volume expansion - longer period - effects lasts for about 24 hrs
• DISADVANTAGES
• No oxygen carrying capacity - hematocrit should not fall below 30%
• METABOLISM & EXCRETION
• Long half life (17days) - misleading - oncotic effects disappear within 24 hrs
80. • USES
FIRST GENERATION HES - HETASTARCH - HES
450/0.7
USES RATE OF INFUSION
Haemorrhagic shock Upto 20 ml/kg
Septic & burn shock Lowered rate of infusion
In children under 10 years Do not exceed 15 ml/kg
81. SECOND GENERATION HES- PENTASTARCH- HAES - STERIL
(200/0.5) -3% , 6%, 10%
• PHARMACOLOGICAL PROPERTIES
• Avg molecular weight--200,000dalton
• Degree of substitution - 0.5 mainly in C2 position
• C2/C6 -5:1
• PHYSIOLOGICAL PROPERTIES
• Effective & safe plasma volume expander
• Contains smaller but more numerous starch molecules than hetastarch - HIGH COP
• More effective as a volume expander than hetastarch- 1.5 times infusion volume depending on concentration
• Oncotic effect reduces after 12 hrs
• Less tendency to interact with coagulation proteins
• Two similar preparations - not similarly degraded by amylase
82. • Effects of HAES-Steril 6%
• following infusion HAES - Steril 6% (500ml/15min) in hypovolemic subjects - 100% volume expansion over 4-8
hrs --> improvement in circulation & microcirculation over a period of atleast 4-8 hrs
• Degraded continuously by serum amylase & eliminated predominantly via the kidneys approx -47% appear in
urine within 24 hr & 10% still detected in plasma
• Effects of HAES- Steril 10%
• Volume expansion 145% over 1 hr& 100% over another 2 hrs
• 54% in urine within 24 hr & 10% still detected in plasma
• BENIFITS
• HAES - Steril 6% maintains normovolemia, normalizes BP, improves hemodynamic condition.
• replaces lost blood volume on 1:1 basis -safe to use in dehydrated patients
• HAES - Steril 10% - fast restoration of blood volume ; shows rapid & strong rise in BP;
• Brings pronounced & reliable volume effects within short time & less volume required to stabilize
hemodynamics
SECOND GENERATION HES- PENTASTARCH- HAES - STERIL
(200/0.5) -3% , 6%, 10%
83. • Indications
• Surgery , trauma, sepsis, burns - hypovolemia - therapy & prophylaxis
• Used to save donor blood during surgery & also for therapeutic dilution of blood.
• RECOMMENDED DOSAGE
1. For intravenous infusion
• Initial 10-20 ml of HAES - Steril 6 % or HAES - Steril 10 % slowly - under closed observation(
possibility of anaphylactoid reaction)
• Daily dose & rate of infusion - acc to blood loss & hemoconcentration
2. Recommended dosage
• Duration & extent of treatment are to be determined according to duration & extent of hypovolemia
SECOND GENERATION HES- PENTASTARCH- HAES - STERIL
(200/0.5) -3% , 6%, 10%
84. • RECOMMENDED DOSAGE
3. Recommended dosage for ANH
• Daily dose : 250ml/day (low)
500ml/day (medium)
2X500ml/day (high)
• Infusion rates :250ml in 0.5-2 hrs → 500ml in 4-6 hrs → 2X 500ml in 8-24 hrs
• ANH -typically used in cardiac surgery & in major orthopaedic surgery
• Unless otherwise prescribed, substitution of autologous blood immediately prior to surgery at target
hematocrit values after ANH not below 30%
• Substitution at a ratio of 1:1 (HAES - Steril 6 %:blood)
• Daily dose 2-3 X 500ml (HAES - Steril 6 %)
• Blood letting 2-3 X 500ml (autologous blood)
• Infusion rates 1000ml/15-30min
• Blood withdrawal rates 1000ml/15-30min
SECOND GENERATION HES- PENTASTARCH- HAES -
STERIL (200/0.5) -3% , 6%, 10%
85. • RECOMMENDED DOSAGE
4. Recommended dosage for hemodilution therapy
• Isovolemic (with blood letting) or hypervolemic (without blood letting) with low (250ml), medium (500ml) or
high dosage (2X500ml)
• Precautions in patients with otoneurological disorders
• Literature suggest - relation between dose & frequency of itching in patients with otoneurological
disorders (deafness, tinnitus or acoustic trauma)
• - reduce dose to a maximum of 500ml/day of HAES - Steril 6 % or 250ml/day of HAES - Steril 10 %.
• Ensure adequate fluid intake
• Hemodilution therapy :recommended for 10 days
SECOND GENERATION HES- PENTASTARCH- HAES -
STERIL (200/0.5) -3% , 6%, 10%
86. • Associated with 15% reduction in blood loss compared to gelatin & pentastarches(10% )
• Pharmacodynamics
• Isovolemic exhange of blood with voluven maintains blood volume for at least 6 hrs
THIRD GENERATION HES : TETRASTARCH
Size of molecule
Alpha -amylase
<70000(renal threshold) 130000
87. • Pharmacokinetics
• Remains 75% of peak concentration at30min
• To 14% at 6 hrs post infusion
• Single dose 500ml -62% elimination in urine in 72 hrs
• INDICATIONS
• treatment of hypovolemia
• Cardiac priming during cardiac surgery
• Pre, intra & post operative volume replacement in all type of surgeries
• Pre loading in spinal anaesthesia
• Blood saving- ANH & AHH
• Burns
• Trauma
• Sepsis
THIRD GENERATION HES : TETRASTARCH
88. • CONTRAINDICATIONS
• Fluid overload ( pulmonary edema & CCF)
• SHOULD NOT BE USED in renal failure with oligura or anuria not related to hypovolemia & in patients
receiving HD
• SHOULD NOT BE USED in severe hypernatremia or severe hyperchloraemia
• Hypersensitivity to HES
• Intracranial bleeding
• Warning & precautions
• Fluid overload
• Severe dehydration- crystalloids to be given first
• Severe liver disease or severe bleeding disorder
• Large volumes administration- transiently alter the coagulation mechanism, decrease hematocrit &
plasma proteins due to hemodilution
• Elevated serum amylase - interfere with diagnosis of pancreatitis
• Supply sufficient fluid and regularly monitor kidney function & fluid balance
• Serum electrolytes to be monitored
THIRD GENERATION HES : TETRASTARCH
89. • ADVERSE REACTION
• anaphylactoid reaction
• Pruritus
• Dilution of blood components such as coagulation factors , plasma proteins & decrease in hematocrit
• Special patients group
• Elderly - risk of renal impairment
• Waxy maize derived tetrastarch HES 130/0.4 - well documented safety profile
• Abdominal surgery in elderly - HES - 130 / 0.4 adequate replacement for albumin & gelatin
• Waxy maize HES - 130 / 0.4 only third generation HES with controlled clinical data in children
THIRD GENERATION HES : TETRASTARCH
91. • Effects on microcirculation& oxygenation by tetrastarch
1. Hypovolemia → stimulation of sympathoadrenergic & RAAS → may result in inadequate tissue perfusion &
oxygen supply to the tissues
2. Benefits of fluid therapy
i. Third generation HES 130/0.4 – positive effects on tissue oxygenation & microcirculation in patients
undergoing major abdominal surgery
ii. Increase tissue oxygenation > crystalloids
iii. Tetrastarch >> pentastarch( 6% HES 70/0.5 & 6% HES 200/0.5) – more increase in tissue oxygen tension
iv. This is due to beneficial effects on microperfusion & reduced endothelial swelling –
v. Crystalloids mostly distribute in interstitium causing endothelial tissue swelling & reduced capillary
perfusion
THIRD GENERATION HES : TETRASTARCH
92. • Dosage & administration
• Why do we prefer HES 130/0.4 (voluven)
• Well characterized plasma expansion
• Large volume can be given(50 ml/kg)
• Minor effects on hemostasis
• Minor influence on renal function
• Relative rapid elimination
• Reduction of endothelial cell activation & inflammatory response
• Minimal risk of anaphylactic reactions
THIRD GENERATION HES : TETRASTARCH
Authors Indication Max dose used
Elliger et al Urosurgery 50 ml/kg
Neff et al Head injury 70 ml/kg
Frey et al Cardiac surgery 48 ml/kg
Kasper et al CABG 50 ml/kg
93. • VOLULYTE – 6% HES 130/0.4 in an ISOTONIC ELECTROLYE SOLUTION
• Avoids hyperchloraemic acidosis which is associated with administration of large volumes of 0.9% saline .
• Composition
• Dosage & administration: indications & contraindications are all same as for Voluven
THIRD GENERATION HES : TETRASTARCH
Sodium 137 mmol/L
Potassium 4 mmol/L
Magnesium 1.5 mmol/L
Chloride 110 mmol/L
Acetate 34 mmol/L
Osmolality 286.5 mOsm/L
pH 5.7-6.5
94.
95. Crystalloids Colloids
Inexpensive Longer intravascular life
Easily available Improves cardiac output
Non-allergenic Opens up the microcirculations
Do not interfere with the coagulation Do not contribute to interstitial edema
Can be rapidly diresed
ADVANTAGES
DISADVANTAGES
Crystalloids Colloids
Larger volumes needed Expensive
Do not carry O2 Anaphylaxis known
Contribute to peripheral & pulmonary edema May interfere with coagulation
Redistribute within an hour Can cause electrolyte imbalance
If capillary endothelium is leaking, pulmonary
edema may occur
96. QUESTIONS ASKED IN EXAMINATION
● Discuss the different types of colloid solutions.Describe their advantages and disadvantages
(June2012)
● Plasma volume expansion(June 1999)(Dec 1999).
● Uses ,advantages and disadvantages of plasma expanders(June 1998).
● Plasma expanders(Dec 2001).
● Plasma volume expanders(June 2005). Comparitive evaluation of RL,Low molecular weight
Dextran and 3.5%poly
● Human Albumin(Dec 2003).Merits and demerits of various synthetic colloids(Dec 2006).
● Discuss the role of plasma proteins in anaesthesia(June 2007).
● Compare and contrast as IV fluid(Dec 2008).
