medication preparation

1. FLUID THERAPY
Presenter : DrAshutosh
DATE: 23-04-2018

2. INTRODUCTION
• In 1861 Thomas Graham’s investigated and classified substances as crystalloids and
colloids depending on their ability to diffuse through a parchment membrane.
Intravenous fluids are similarly classified based on their ability to pass through capillary
walls that separate the intravascular and interstitial fluid compartments
• Crystalloid fluids are electrolyte solutions with small molecules that can diffuse freely
from intravascular to interstitial fluid compartments
• Colloid fluid is a saline solution with large solute molecules that do not pass readily
from plasma to interstitial fluid. The retained molecules in a colloid fluid create an
osmotic force called the colloid osmotic pressure or oncotic pressure that holds water in
the vascular compartment

3. COMPOSITION OF BODY FLUIDS
• Water is the most abundant constituent in the body, comprising approximately
50% of body weight in women and 60% in men
• 55–75% is intracellular [ICF] and 25–45% is extracellular [ECF]
• The ECF is further subdivided into intravascular (plasma water) and extravascular
(interstitial) spaces in a ratio of 1:3
• Fluid movement between the intravascular and interstitial spaces occurs across the
capillary wall and is determined by Starling forces, i.e., capillary hydraulic
pressure and colloid osmotic pressure

4. • Principal component of extracellular
fluid is Sodium  responsible for
much of extracellular fluid
osmolality
• Principal component of intracellular
fluid is Potassium key role in the
maintenance of transmembrane
potentials

5. The aims of IV fluid administration should be to
• Avoid dehydration
• Maintain an effective circulating volume
• Prevent inadequate tissue perfusion during a period when the patient is unable to
achieve
These goals through normal oral fluid intake
“Intravenous fluids have a range of physiologic effects and should be considered to
be drugs with indications, dose ranges, cautions, and side effects.”

7. CLASSIFICATION
I V Fluids
Blood and Products Non blood I V Fluids
Crystalloids
•Glucose Containing
•Electrolyte
solutions
•Mixed
Colloids
Proteinous Non proteinous
Gelatins
• Haemaccel
• Gelofusin
Albumin
20% & 5%
Starch Dextrans
 HES
 PentaStarch
 Tetrastarch

8. CRYSTALLOIDS

9. CRYSTALLOIDS
Crystalloid are electrolyte solutions with small molecules that can diffuse freely
intravascular to interstitial fluid compartments
from
• The principal component of crystalloid fluids is sodium chloride. Sodium is the
principal determinant of extracellular volume, and is distributed uniformly in the
extracellular fluid
• Because the plasma volume is only 25% of the interstitial fluid volume only 25% of an
infused crystalloid fluid will expand the plasma volume, while 75% of the infused
volume will expand the interstitial fluid.
• Thus, the predominant effect is only 25% of transfused crystalloids remains in the
intravascular space and 75% diffuses into interstitial space

10. General characteristics of Crystalloid
• Contains water and electrolytes
• Non ionic solutions expands
extracellular space
all the compartments i.e intracellular and
• Sodium cannot gain access into the intracellular space. Hence all sodium will
remain in the extracellular space thus expanding it

11. The effects of selected colloid and crystalloid fluids on the plasma volume and
interstitial fluid volume

12. CRYSTALLOIDS
HYPOTONIC ISOTONIC HYPERTONIC IONIC NON-IONIC
• D5W
• ½ NS(0.45%)
• NS
• RL
• Plasmalyte
• Hypertonic
saline
• 10%, 25% &
50% dextrose.
• NS
• Dextrose saline
(DNS)
• Ringer’s lactate
• 5% Dextrose
• 25% Dextrose

13. NORMAL SALINE
• One of the most commonly administered crystalloids
• Using in vitro red cell lysis experiments, Hamburger ascertained that 0.9% was
the NaCl concentration that was isotonic with human plasma. It was not initially
developed with the aim of in vivo administration, yet has entered widespread
clinical use despite having a Na+ and Cl− concentration far in excess of that of
plasma
• 0.9% saline also known as normal saline, physiological saline, isotonic saline - but
none of these names are appropriate as chemically it is not normal because the
concentration of a one-normal (1 N) NaCL solution is 58 grams per liter (the
combined molecular weights of sodium and chloride), while 0.9% NaCL contains
only 9 grams of NaCL per liter

14. • Composition
Na-154 meq/l
Cl- 154 meq/l
pH- 5.7
hence it affects the acid base balance of the body
• Pharmacological basis
1. Provide major extracellular electrolytes.
2. Corrects both water and electrolyte deficit.
3. Increase the intravascular volume substantially.

15. Volume effects of NS
• Infusion of one liter of 0.9% NaCL adds 275 mL to the plasma volume and 825 mL to
the interstitial volume
• one unexpected finding; i.e., the total increase in extracellular volume (1,100 mL) is
slightly greater than the infused volume. This is the result of a fluid shift from the
intracellular to extracellular fluid, which occurs because 0.9% NaCL is slightly
hypertonic in relation to Extracellular fluid
Acid-Base Effect
• Large-volume infusions of 0.9% NaCL produce a metabolic acidosis
• The saline-induced metabolic acidosis is a hyperchloremic acidosis, and is caused by
the high concentration of chloride in 0.9% saline relative to plasma (154 versus 103
mEq/L)

16. Interstitial edema
Promote interstitial edem more than other crystalloid fluids with a lower sodium
content (e.g., Ringer’s lactate, Plasma-Lyte) through
1. Increased sodium load from 0.9% NaCL, which increases the “tonicity” of
the interstitial fluid
2. Sodium retention by suppressing the renin-angiotensin-aldosterone axis
3. Decreases in renal perfusion have also been observed after infusion of 0.9%
NaCL,presumably as aresult of chloride-mediated renal vasoconstriction.

17. STRONG ION DIFFERENCE (SID)
• It is the difference between strongest cation and strongest anion in a particular
compartment.
• Electrical neutrality needs cation = anions
Strong ion difference + [H+] – [OH-] = 0
• Since hydroxyl ion is negligible ,
Strong ion difference + [H+] = 0
• normal SID = Na – Cl
= 140 – 103
= 40 meq/ litre

18. • Strong ion difference + [H+] = 0
• therefore, if SID increases , [H+] decreases to maintain electrical neutrality.
• In 0.9% NaCl , SID=0
• Hence [H+] increases = pH decreases = acidosis.
• The SID of intravenous fluids determines their ability to influence the pH of
plasma. The SID of 0.9% NaCL is zero (Na – CL = 154 – 154 = 0) , so infusions
of 0.9% NaCL will reduce the SID of plasma and thereby reduce the plasma pH.
The SID of Ringer’s lactate fluid is 28 mEq/L (Na + K + Ca – CL= 130 + 4 + 3 –
109 = 28) if all the infused lactate is metabolized

19. Indications
• To maintain effective blood volume and blood pressure in emergencies
• Water and salt depletion – diarrhoea, vomiting, excessive diuresis or excessive perspiration
• Hypovolemic shock- distributed in extracellular space expanding the intravascular volume.
Ideal fluid to increase blood pressure.
• Preferred in case of brain injury, hypochloraemic metabolic alkalosis , hyponatraemia
• Initial fluid therapy in DKA
• In patients with hyperkalemia like renal failure
• Hypercalcaemia
• Fluid challenge in prerenalARF
• Irrigation for washing of body fluids
• Vehicle for certain drugs

20. Limitations/ Contraindications
• Avoid in Hypertension, Preeclamsia and in patient with edema due to CCF, renal
failure and cirrhosis
• In dehydration with severe hypokalaemia – deficit of intracellular potassium –
infusion of NS without additional K+ supplementation can aggravate electrolyte
imbalance
• Large volumes or too rapid administration can cause sodium accumulation and
pulmonary edema.
• Increased chloride content in relation to plasma can cause hyperchloremic
metabolic acidosis in large volume administration

21. RINGER'S FLUIDS
• In 1880, Sydney Ringer , a British physician studied the contraction of isolated
frog heart
• He introduced a solution that contained calcium and potassium in sodium chloride
solution to promote cardiac contraction and cell viability. This is known as
Ringer`s injection
• In early 1930, an American pediatrician named Alex Hartmann added sodium
lactate to Ringer`s solution as a buffer to metabolic acidosis
• This is known as Hartmann`s solution or Ringer`s lactate

22. Composition
• Ion concentration RL
Sodium:131meq/l
Potassium – 5meq/L
Bicarbonate – 29 meq/L
Chloride – 111meq/L
Calcium – 2meq/L
• Each 100 ml contains
sodium lactate - 320mg
NaCl - 600mg,
KCl- 40mg
CaCl- 27mg

23. Advantage :
• Lack of significant effect on acid base balance
Disadvantage:
• Presence of ionized calcium in ringer’s lactate can binds to citrated anticoagulant in
stored blood and promote formation of clots. (clot formation does not occur if the
volume of Ringer’s solution does not exceed 50% of the volume of packed RBCs)
• In critically ill patients with impaired lactate clearance due to circulatory shock or
hepatic insufficiency, Ringer’s lactate infusion can increase serum lactate levels

24. Pharmacological basis
• Ringer`s lactate is the most physiological fluid as the electrolyte content is similar
to that of plasma . Larger volumes can be infused without the risk of electrolyte
imbalance
• Due to high Na ( 130mEq/L) content RL rapidly expands intravascular volume
effective in treatment of hypovolemia
• Sodium lactate in RL is metabolized to bicarbonate in the liver -- useful in
correction of metabolic acidosis

25. Indications :
• Correction in severe hypovolaemia
• Replacing fluid in post operative patients, burns , fractures.
• Diarrhoea induced hypokalemic metabolic acidosis and hypovolemia.
• Fluid of choice in diarrhoea induced dehydration in paediatric patients.
• In DKA , provides glucose free water, correct metabolic acidosis and supplies
potassium
• Maintainance fluid during surgery

26. Contraindications
• Severe liver disease, severe hypoxia , shock – impaired lactate metabolism –lactic
acidosis.
• Severe CHF - lactic acidosis takes place.
• Addison’s disease
• In vomiting or continuous nasogastric aspiration, hypovolemia is associated with
metabolic alkalosis - as RL provides HCO3- Worsens alkalosis.
• Simultaneous infusion of RL and blood- inactivation of anticoagulant by binding
with calcium in RL – clots in donor blood.
• Certain drugs – amphotericin, thiopental, ampicillin, doxycycline should not be
mixed with RL – calcium binds with these drugs and reduces bioavailability and
efficiency

27. DEXTROSE SOLUTIONS
• D5 water (5%D)
• Dextrose with 0.9% NS ( DNS ).
• Dextrose with 0.45% NS (D 1/2NS )
• 10% dextrose
• 25% dextrose
EFFECT OF DEXTROSE IN FLUID :
Protein sparing effects
Volume effect
Lactate production.
Effect of hyperglycemia

28. Protein sparing effect
• Earlier it was used to provide calories in patients who were unable to eat
• 50 grams of dextrose per liter provides 170 kcal
• Infusion of 3 liters of a D5 solution daily (125 mL/min) provides 3 x 170 = 510
kcal/day, which is enough nonprotein calories to limit the breakdown of
endogenous proteins to provide calories (i.e., protein-sparing effect)
• It is no longer used frequently as most patients with long-term Nil by mouth have
enteral tube feedings or TPN

29. Volume Effects
5%D
• 50 g of dextrose adds 278 mOsm/L to IV fluids
• For a 5% dextrose the added dextrose brings the osmolality close to that of plasma.
However, dextrose is taken up by cells and metabolized, this osmolality effect rapidly
wanes, and the added water then moves into cells.
• The infusion of one liter of 5D results in an increase in ECF (plasma plus interstitial
fluid) of about 350 mL, which means the remaining 650 ml (two-thirds of the infused
volume) has moved intracellularly. Therefore, the predominant effect of D5W is cellular
swelling.
 DNS
• Total osmolality of DNS fluid is 560 mOsm/L (278 of dextrose and 308 0f 0.9 NaCl)
which is almost twice the normal osmolality of the extracellular fluid. If glucose
utilization is impaired (as is common in critically ill patients), large-volume infusions
of D5W can result in cellular dehydration

30. Enhanced lactate production
• In healthy individuals 5% of infused glucose is directed towards lactate formation.
• In critically ill patients 85% of glucose is diverted to lactate production.
• when circulatory flow is compromised, infusion of 5% dextrose solutions can result in lactic
acid production and significant elevations of serum lactate
Hyperglycemia
It has several deleterious effects in critically ill patients including –
• immune suppression .
• increased risk of infection .
• aggravation of ischemic brain injury
Considering the high risk of hyperglycemia in ICU patients, and the numerous adverse
consequences of hyperglycemia, infusion of dextrose containing fluids should be avoided
whenever possible.

31. 5 % DEXTROSE
Composition : Glucose 50 gms/L + free water
Pharmacological Basis
•Corrects DehydrationAnd Supplies Energy ( 70kcal/L)
•Administered safely at the rate of 0.5gm/kg/hr without causing glycosuria
Metabolism
 Dextrose is metabolised leaving free water  distributed in all compartments of the
body.
 Aproportion of dextrose load contributes to lactate formation –
 5% in healthy subjects
 85% in critically ill patients ----hence not the preferred fluid.

32. Indications of 5%D
• Prevention and treatment of intracellular dehydration
• Cheapest fluid to provide adequate calories to body
• For pre and post operative fluid management
• IV administration of various drugs
• Treatment and Prevention of ketosis in starvation, vomiting, diarrhoea
• Adequate glucose infusion protects liver against toxic substances.
• Correction of hypernatraemia due to pure water loss ( Diabetes insipidus)

33. Limitations of 5D
1. Neurosurgical procedures - can aggravate Cerebral oedema and increase ICT
2. Acute ischaemic stroke-
• hyperglycemia aggravates cerebral ischaemic brain damage.
• Dextrose metabolism aggravates tissue acidosis in ischaemic areas- anerobic oxidation
of glucose produces more lactic acid and free radicals
3. Hypovolemic shock
• Poor expansion of intracellular volume.
• Faster rate of infusion causes osmotic diuresis  worsens shock and false impression
of the hydration status  reduced fluid replacement.
4. Hyponatremia & water intoxication - 5%D worsens both conditions

34. Limitations of 5D
5. Hypernatremia – fast infusion of 5D rapidly corrects hypernatremia but correction
occurs slowly in brain cells, so swelling of brain cells can lead to permanent
neurological damage. Moreover rapid infusion of 5D induces osmotic diuresis
which aggravates hypernatremia
6. Can cause Hypokalemia, hypomagnesemia and hypophosphatemia
7. Blood and dextrose solutions should not be administered in same IV line –
haemolysis , clumping seen due to hypotonicity of the solution.
8. Uncontrolled DM , severe hyperglycemia

35. DEXTROSE SALINE (DNS)
Composition
Na- 154 mEq/L
CI- 154mEq/L
Glucose- 50 gm/L
Pharmacological basis
• supply major extracellular electrolytes, energy and fluid to correct dehydration
• In presence of incompletely or partially corrected shock patient will have increased
urine output (due to diuresis)
• Unlike 5D, DNS is not hypotonic (due to Nacl) and hence it is compatible with blood
transfusion

36. Indications
• Conditions with salt depletion and hypovolaemia - not the ideal fluid though.
Faster rate of infusion causes osmotic diuresis  worsens shock and false
impression of the hydration status  reduced fluid replacement
• Correction of vomiting or nasogastric aspiration induced alkalosis and
hypochloremia along with supply of calories
Limitations
• Anasarca – cardiac, hepatic or renal cause
• Severe hypovolemic shock – rapid correction is needed. Faster infusion can cause
osmotic diuresis and worsen the condition

37. DEXTROSE WITH HALF STRENGTH SALINE
•Composition : 5% dextrose with 0.45% NS NaCl – 77 meq/L each, glucose 50 gm/L
• Contains 50% salt as compared to DNS /NS and used when there is need for calories ,
more water and less salt.
•Indications
1. Fluid therapy in paediatric – In paediatric group ratio of requirement of water : NaCl
is double as compared to adults
2. Treatment of severe hypernatremia – It corrects hypernatremia gently, it avoids
cerebral edema
3. Maintenance fluid therapy and in early post operative period.
•Limitations
1. Hyponatremia
2. Severe dehydration where larger salt replacement is needed

38. 10% DEXTROSE & 25% DEXTROSE
Composition
1 liter of 10%D has 100 gms glucose
1 liter of 25%D has 250 gms glucose
Pharmacological basis:
• It is hypertonic crystalloid fluid
• Supplies energy and prevents catabolism  useful when faster replacement of glucose is
needed like in Hypoglycemic coma
• In patients with fluid restriction- CCF, Cirrhosis and Renal failure

39. Indications
• Rapid correction of hypoglycaemia .
• In liver disease, if given as first drip, it inhibits glycogenolysis and gluconeogenesis
• Nutrition to patients on maintainance fluid therapy.
• Treatment of hyperkalemia with Insulin
Limitations
• In patients with dehydration , anuria , intracranial hemorrhage
tremens
• Avoided in patients with diabetes unless there is hypoglycemia.
• Rapid infusion of 25D can cause glycosuria . Hence in
hypoglycemia it should be infused slowly over 45 - 60 min
and in delirium
the absence of

40. HYPEROSMOLAR FLUIDS
MANNITOL
HYPERTONIC SALINE

41. MANNITOL
• Mannitol is an osmotic diuretic that is metabolically inert in humans
• Mannitol elevates blood plasma osmolality, resulting in enhanced flow of
water from tissues, including the brain and cerebrospinal fluid, into interstitial
fluid and plasma
• As a result cerebral edema, elevated intracranial pressure, and cerebrospinal
fluid volume and pressure may be reduced
• Benificial effects are due to the reduction in blood viscosity
• Complications associated are
• Rebound edema
• Dehydration due to osmotic diuresis
• Renal failure

42. Limitations
• Anuria due to severe renal disease
• Cannot be used in patients with hypotension
• Severe pulmonary congestion or frank pulmonary edema
• Active intracranial bleeding except during craniotomy
• Severe dehydration
• Progressive renal damage or dysfunction after institution of mannitol therapy,
including increasing oliguria and azotemia

43. HYPERTONIC SALINE
• Available as 1.8%, 3% , 5%, and 7.5%

44. PHARMACOLOGICALPROPERTIES
The hypertonic nature of these solutions draws water out of the intracellular
compartment into the extracellular compartment
USES
•Plasma volume expansion: The hypertonic nature of these solutions draws water
out of the intracellular compartment and into the extracellular (including plasma)
volume and may therefore achieve plasma volume expansion while minimizing the
volume of fluid administered. However, clinical trials have not shown any benefits.
• Correction of hypo osmolar hyponatremia
• Treatment of raised ICT - superior to mannitol
• 7.5% - endothelial injury  used as sclerosant

45. Isolyte G,M,P,E
ISOLYTE G ISOLYTE M ISOLYTE P ISOLYTE E
DEXTROSE 50 50 50 50
Na 63 40 25 140
K 17 35 20 10
Cl 150 40 22 103
Acetate --- 20 23 47
Lactate --- --- --- ---
NH4CL 70 --- --- ---
Ca --- --- --- 5
Mg --- --- --- 3
HPo4 --- 15 3 ---
Citrate --- --- 3 8
Mosm/L 580 410 368 595

46. INDICATIONS AND LIMITATIONS
Isolyte G :
Vomiting / NGT induced hypochloremic , hypokalemic metabolic alkalosis.
NH4 gets converted to H+ and urea in the liver.
Treatment of metabolic alkalosis.
Limitations : hepatic failure , renal failure , metabolic acidosis
ISOLYTE M:
Richest source of potassium (35mEq)
correction of hypokalaemia.
LIMITATIONS : Renal failure ,burns, adrenocortical insufficiency.

47. ISOLYTE P:
Maintenance fluid for children.
Excessive water loss or inability to concentrate urine .
LIMITATIONS : hyponatremia , renal failure.
ISOLYTE E:
Extracellular replacement fluid, additional potassium and acetate.
Corrects Mg deficiency.
Treatment of diarrhoea and metabolic acidosis.
LIMITATIONS : metabolic alkalosis.

48. PLASMA-LYTE
• Ionic concentration of 1 litre Na+- 140 mEq ,K+- 5 mEq ,Mg2+ - 3 mEq, Cl- --98 mEq ,
27 mEq acetate, and 23 mEq gluconate with a pH of 7.4.
• The caloric content is 21 kcal/L.
• Each 100 mL contains - 526 mg of NaCl; 502 mg of Sodium Gluconate; 368 mg of Sodium
Acetate Trihydrate; 37 mg of KCl and 30 mg of Magnesium Chloride.
• Osmolarity  295 mOsmol/L .
• Acetate and gluconate ions are metabolized ultimately to carbon dioxide and water, which
requires the consumption of hydrogen cations  alkalinizing effect.
• Caution : in patients with hyperkalemia, severe renal failure, and in conditions in which
potassium retention is present.

50. COLLOIDS

51. COLLOIDS
• The term colloid is derived from Greek word “Glue”.
• These solutions are also called suspensions
• Colloid fluid is a saline fluid with large solute molecules that do not readily pass
from plasma to interstitial fluid.
• Colloids have large molecular weight >30000 Daltons that largely remain in
intravascular compartment.
• The retained molecules create an osmotic force called colloidal osmotic pressure
or oncotic pressure.
• In normal plasma the plasma proteins are the major colloids present

52. General characteristics of colloids
This characteristic determines their behaviour in the intravascular compartment
1. Molecular weight.
2. Colloid molecular size- monodisperse and polydisperse
3. Plasma volume expansion- determined by the molecular weight.
4. Osmolality.
5. Colloid osmotic pressure – determines the volume of expansion.
6. Plasma Half Life- depends on the molecular weight and the route of
elimination.
7. Electrolyte content – Na content.
8. Acid base composition – albumin and gelatin have physiologic pH, others are
acidic

53. Capillary fluid Exchange
• The direction and rate of fluid exchange (Q) between capillary blood and interstitial
fluid is determined, in part, by the balance between the hydrostatic pressure in the
capillaries (Pc), which promotes the movement of fluid out of capillaries, and the colloid
osmotic pressure of plasma (COP), which favors the movement of fluid into capillaries.
Q ≈ PC – COP
• Normal Pc averages about 20 mm Hg (30 mm Hg at the arterial end of the capillaries
and 10 mm Hg at the venous end of the capillaries); the normal COP of plasma is about
28 mm Hg, so the net forces normally favor the movement of fluid into capillaries
(which preserves the plasma volume)
• About 80% of the plasma COP is due to the albumin fraction of plasma proteins

54. Resuscitation Fluids
• Crystalloid fluids reduce the plasma COP (dilutional effect), which favors the
movement of these fluids out of the bloodstream
• Colloid fluids can preserve the normal COP (iso-oncotic fluids), which holds these
fluids in the bloodstream, or they can increase the plasma COP (hyperoncotic
colloid fluids), which pulls interstitial fluid into the bloodstream

55. CHARACTERISTICS OF I.V. COLLOIDS FLUIDS PER 100ML INFUSION
Colloid fluid is about 3 times more effective in expanding the plasma volume than
the crystalloid fluid
FLUID TYPE ONCOTIC PRESSURE
(mmHg)
PLASMA VOLUME
EXPANSION
DURATION OF
EFFECT
5% Albumin 20 70-130 ml 12 h
25% albumin 70 400-500 ml 12 h
10% Dextran-40 40 100-150 ml 6 h
6% Dextran -70 80 ml 12 h
6% Hetastarch 30 100-130 ml 24 h
10% Pentastarch 150 ml 8 h

56. COLLOIDS
Natural
colloids
Artificial
colloids
Albumin 5%,20%
25%
Fresh Frozen
Plasma
Plasma proteins
4% 5%
Dextrans
Gelatins
HES

57. ALBUMIN
• Albumin is a versatile plasma protein synthesized only in the liver and has a half-life of
approximately 20 days.
• Principal determinant of plasma colloid osmotic pressure COP ( 75% of the oncotic
pressure), principal transport protein in blood, has significant antioxidant activity, and
helps maintain the fluidity of blood by inhibiting platelet aggregation
• 5% albumin ( 50gm/L or 5gm /dl) has COP of 20 mmHg (similar to plasma) & expands
plasma volume to same as volume infused
• 25% albumin ( 250gm/L or 25gm /dl) has COP of 70 mmHg & expands plasma volume
by 4 to 5 times the infused volume
In adults – Initial Infusion Of 25 gm
1 To 2 ml/min – 5%Albumin
1 ml/min - 25%Albumin

58. Indications:
• Emergency treatment of shock specially due to the loss of plasma.
• Acute management of burns
• Fluid resuscitation in intensive care
• Clinical situations of hypo-albuminemia
I. Following paracentesis.
Ii. Patients with liver cirrhosis.
Iii.After liver transplantation.
• Spontaneous bacterial peritonitis
• Acute lung injury
• Correction of diuretic resistant nephrotic syndrome
• In therapeutic plasmapheresis, albumin is used as an exchnage fluid to replace
removed plasma

59. Precautions and contraindications
• Because it does not replace lost volume, but instead shifts fluid from one
compartment to another, 25% albumin should not be used for volume resuscitation
in patients with blood loss
• 5% albumin is safe to use as a resuscitation fluid, except possibly in traumatic
head injury
• Hyperoncotic (25%) albumin has been associated with an increased risk of renal
injury and death in patients with circulatory shock
• Fast infusion will rapidly increase circulatory volume with resultant vascular
overload and pulmonary oedema
• Contraindicated in severs anaemia and cardiac failure
• Dehydrated patient may require additional fluids along with albumin
• Should not be used as parenteral nutrition

60. Disadvantages
1. Cost effectiveness:Albumin is expensive as compared to synthetic colloids
2.Volume overload: In septic shock the release of inflammatory mediators has been
implicated in increasing the ‘leakiness’ of the vascular endothelium. The
administration of exogenous albumin may compound the problem by adding to the
interstitial edema.

61. GELATIN POLYMERS( HAEMACCEL)
• Gelatin is a large molecular weight protein formed from hydrolysis of bovine
collagen.
• Gelatin solutions were first used as colloids in man in 1915.
• The MW ranges from 5,000 to 50,000 with a weight average MW of 35,000.
3 types of gelatin solutions-
• Succinylated or modified fluid gelatins (e.g.,Gelofusine, Plasmagel, Plasmion)
• Urea-crosslinked gelatins (e.g., Polygeline)
• Oxypolygelatins (e.g., Gelifundol)

62. Physiochemical properties:
• Both succinylated gelatin and polygeline are supplied as preservative-free, sterile solutions
in sodium chloride.
• Polygeline is supplied as a 3.5% solution
• electrolytes (Na+ 145, K+ 5.1, Ca++ 6.25 & Cl- 145mmol/l) .
Metabolism:
• It is rapidly excreted by the kidney.
• Peak plasma concentration falls by half in 2.5 hours.
• duration of action is shorter in comparison to both albumin and starches
Indications :
• Rapid Plasma Volume Expansion In Hypovolemia
• Volume Pre Loading In RegionalAnaesthesia
• Priming Of Heart Lung Machines

63. Advantages:
• Cost effective: It is cheaper as compared to albumin and other synthetic colloids.
• No limit of infusion: Gelatins do not have any upper limit of volume that can be
infused as compared to both starches and dextrans.
• Less effect of renal impairment: Gelatins are readily excreted by glomerular
filtration as they are small sized molecules.
Disadvantages:
• Anaphylactoid reactions: Gelatins are associated with higher incidence of
anaphylactoid reactions as compared to natural colloid albumin.

64. HYDROXYETHYL STARCH
• Hydroxyethyl starch (HES) is a chemically modified polysaccharide composed of
long chains of branched glucose polymers substituted periodically by hydroxyl
radicals (OH), which resist enzymatic degradation
• HES elimination involves hydrolysis by amylase enzymes in the bloodstream,
which cleave the parent molecule until it is small enough to be cleared by the
kidneys
• HES are derivatives of amylopectin, which is a highly branched compound of
starch

65. Physiochemical Properties
1.Concentration: low (6%) or high (10%).
Concentration mainly influences the initial volume effect:
• 6% HES solutions are iso-oncotic
• 10% solutions are hyperoncotic
2. Average Molecular Weight (MW):
• low (70 kDa),
• medium ( 200 kDa)
• high ( 450 - 480 kDa)

66. 3. Molar substitution (MS)
• low (0.45-0.58) or high (0.62-0.70)
• The degree of substitution refers to the modification of the original substance by the
addition hydroxyl radical
•
• The higher the degree of molar substitution --- the greater the resistance to degradation
and longer half life of colloid
• MS is thus the average number of hydroxyethyl residues per glucose subunit
• Names are applied to describe other levels of substitution: hetastarch
hexastarch (MS 0.6), pentastarch (MS 0.5), and tetrastarch (MS 0.4)
(0.7),

68. Indications
a) Stabilization of systemic haemodynamics
b) Anti-inflammatory properties: HES has been shown to preserve intestinal
microvascular perfusion in endotoxaemia due to their anti-inflammatory properties
Advantages
1.Cost effectiveness: HES is less expensive as compared to albumin and is associated
with a comparable volume of expansion.
2.Maximum allowable volume: Maximum volume which can be transfused of medium
weight HES (130 kDa) with medium degree of substitution (0.4)
is greater as compared to other synthetic colloids like dextrans.
3.The estimated incidence of anaphylactic reactions is less compared to other colloids.

69. Disadvantages
• Increase in Serum amylase concentration during and 3-5 days after discontinuation
• Affects coagulation by prolonging PTT, PT and bleeding time by lowering
fibrinogen , decrease platelet aggregation , VWF , factor VIII
• HES products with medium to high MW are associated with oliguria, increased
creatinine, and acute kidney injury in critically ill patients with preexisting renal
impairment
• Occumulates in reticuloendothelial system and causes pruritis

70. DEXTRAN
• Dextrans are highly branched polysaccharide molecules which are
available for use as an artificial colloid
• These glucose polymers are produced by bacterium (leuconostoc
mesenteroides) incubated in sucrose medium by bacterial dextran
sucrase
Physicochemical properties
• Two dextran solutions are now most widely used,
 6% solution with an average molecular weight of 70,000 (dextran 70)
10% solution with an average weight of 40,000 (dextran 40, low-
molecular-weight dextran).

71. Pharmacological basis
• Effectively expand intravascular volume -- dextran 40 produces greater plasma
expansion than dextran-70 but short duration( 6hrs) and rapid renal excretion
• Anti thrombotic effect - inhibits platelet aggregation
• Improves micro circulatory independently of volume expansion by by decreasing
the viscosity of blood by haemodilution and by inhibiting erythrocytic
aggregation
Metabolism & Excretion
• Kidneys primarily excrete dextran solutions
• Smaller molecules (14000-18000 kda) are excreted in 15minutes whereas larger
molecules stay in circulation for several days
• Up to 40% of dextran-40 and 70% of dextran-70 remain in circulation at 12 hrs.

72. Degree of volume expansion
• Both dextran preparations have a colloid osmotic pressure of 40 mm Hg, and
cause a greater increase in plasma volume than either 5% albumin or 6%
hetastarch. Dextran-70 may be preferred because the duration of action (12 hours)
is longer than that of dextran-40
•
Indications
• Improves microcirculatory flow in microsurgical re-implantations alsoand used for
DVT prophylaxis
• Extracorporeal circulation: It has been used in extracorporeal circulation during
cardio-pulmonary bypass
• Correction of hypovolemia – from burns, surgery, trauma. There is 100- 150%
increase in intravascular volume.

73. Contraindications
• Severe oligo-anuria and renal failure
• Severe CHF
• Bleedind disorders- Thrombocytopenia, hypofibrinogenemia…
• Severe dehydration
• Known hypersensitivity to dextran
Precautions
• Administered with caution in CLD, Impaired renal function ( osmotically mediated
renal injury), active haemorrhage
• Correct dehydration before or during dextran infusion to preventARF
• Dextrans coat the surface of red blood cells and can interfere with the ability to cross-
match blood
• Anticoagulant effect of heparin is enhanced
• Dextrans produce a dose-related bleeding tendency-- impaired platelet aggregation,
decreased levels of Factor VIII and von Willebrand factor, and enhanced fibrinolysis.
The hemostatic defects are minimized by limiting the daily dextran dose to 20 mL/kg.

74. COLLOID ALBUMIN HETASTARCH TETRASTARCH
COST EXPENSIVE CHEAP EXPENSIVE
USE LONG TERM SHORT TERM ANY
COAGULATION NO INCREASED
BLEEDING
RENAL
TRANSPLANTATION
PERIOPERATIVE
NO INCREASED INCREASED BLEEDING
BLEEDING
SAFE PREDISPOSES TO ARF NO EVIDENCE OF RISK
TILL DATE
PRE EXISTING IMPAIRMENT
RENAL SAFE OSMOTIC NEPHROSIS LIKE
LESIONS
NO EVIDENCE OF RISK
TILL DATE.
HEPATIC SAFE ASCITIS,ACCUMULATION NO EVIDENCE OF RISK
TILL DATE

75. FLUIDS IN SPECIFIC CONDITIONS

76. HYPOVOLEMIC SHOCK
Isotonic saline (NS) is selected as an initial fluid because
1 litre of NS will expand intravascular volume by 300ml
Unknown glycemic status (Dextrose solutions will rise glucose level rapidly)
Unknown renal status – RL can cuase hyperkalemia or lactic acidosis
Reaction free (compared to colloids), Least expensive and readily available
RL is preferred IV fluid after urine out is established
RL is most physiological fluid, so large volume can be infused without
electrolyte imbalance
In shock hepatic conversion of lactate to bicarbonate is unpredictable
1 Litre FLUIDS ECF - Intravascular ECF- Interstitial ICF
NS 300 ml 700 ml NIL
5%D 83 ml ( 75-100) 260 670
COLLOIDS 1000 ml

77. Colloids in Hypovolemic shock
More effective plasma expanders as these agents are restricted to intravascular
compartments
Lesser risk of pulmonary oedema
Primary indication is hypotension in protein losing state –burns
Although used in shock , they offer little or no advantages over crystalloids
Blood in hypovolemic shock
In patients who are bleeding
 SevereAnaemia
However with blood transfusion haematocrite should not be raised over 35% -
increase in blood viscosity lead to stasis

78. SEPSIS
• Cardiovascular instability may be a particular problem, contributed by
• endothelial dysfunction
• intravascular fluid loss
• vasodilation with fluid maldistribution
• sympathetic redistribution of blood volume away from the peripheral circulation,
and
• impairment of cardiac function
• Fluid resuscitation, with the goal of maintaining adequate end-organ perfusion is
therefore a key part of the first 6 hours of sepsis treatment.

79. • Targets suggested for patients with sepsis who have tissue hypoperfusion, defined by
blood lactate concentration >4 mmol/L or hypotension persisting after initial IV fluid
challenge:
• CVP 8 to 12 mm Hg (12 to 15 mm Hg in patients on ventilation)
• MAP 65 mm Hg or greater
• Urine output 0.5 mL/kg/hr or greater
• Scvo2 greater than 70%
• In the critical care setting, the use of colloids as resuscitation fluid has been the
subject of a number of important recent publications, which have led to the
withdrawal of HES.
• The crystalloid versus hydroxyethyl starch (CHEST) trial compared the use of
starches for resuscitation with crystalloids and showed not only no survival benefit
with the use of starch but also increased risk ofAKI.

80. • The use of expensive synthetic colloids is difficult to justify as there is a failure to
identify a mortality benefit associated with their use
• However, if the endothelial glycocalyx is impaired (as it is in severe sepsis), then
intravascular retention of any colloid may be no better than that of crystalloid.
• In patients with established acute respiratory distress syndrome (ARDS)- the focus
of fluid therapy is the fine balance between avoiding an increase in lung edema
while maintaining adequate tissue perfusion.
• Amore conservative approach has proven beneficial over liberal fluid therapy
• However, there is a lack of adequately powered studies on the choice of colloid or
crystalloid for intravascular volume replacement in patients withARDS.

81. RECOMMENDATIONS
• Guidelines on IV fluid therapy published by the National Institute for Health and
Care Excellence (NICE) recommend the use of crystalloid solutions containing a
sodium concentration in the range of 130– 154 mmol litre for i.v. fluid resuscitation,
and recommend against the use of tetrastarch for this purpose
• Current recommendations are to use 30 mL/kg of crystalloid in a protocolized
fashion to achieve the described targets
• In patients requiring further fluid, albumin should be considered, along with
vasopressors, inotropes, and RBC transfusion to attain these goals.

82. FLUID CHALLENGE
• The fluid challenge is considered the gold standard for diagnosis of fluid
responsiveness.
• The volume of fluid infused must be sufficient to increase right ventricular diastolic
volume and subsequently stroke volume (SV) as described by the Frank-Starling law.
• Fluid responsiveness is conventionally defined as an increase of at least 10% to 15%
in SV in response to a fluid challenge.
• Patients who reach this threshold are considered ‘fluid responders’.
• The duration of the fluid infusion in a fluid challenge has a significant influence on
fluid responsiveness.
• The proportion of patients deemed to respond to a fluid challenge is influenced by
the characteristics of a fluid challenge technique, in addition to intravascular filling,
vascular tone or ventricular contractility.

83. A4-step process for giving a fluid challenge involves consideration of
Type of fluid- No ideal intravenous fluid solution, crystalloids usually used.
Rate of administration - modified depending upon the patient and underlying disease
process . It is important to define the amount of fluid to be given over a defined interval
(eg: 250- 1000mL of crystalloids over 30 minutes) .
In whom to do fluid challenge test.?
Hypotension secondary to hypovolaemia - clinically demonstrated by a MAP <
65mmHg - 70mmHg.
Tachycardia due to hypovolaemia.
Low urine output secondary to hypovolaemia when urine output is less than 0.5
mL/kg/hr (lean body mass), for a period of at least 2 consecutive hours.
Low cardiac output secondary to low filling pressures in patients with invasive
haemodynamic monitoring.

84. Safety Limits
•Monitor for signs of pulmonary oedema secondary to fluid overload, which is a
serious complications of fluid administration.
• Monitor CVP trends as a safety limit in patients who do not have intrinsic heart or
lung disease to guide therapy.
•More invasive haemodynamic monitoring with a pulmonary artery catheter may be
considered in patients with intrinsic heart or lung disease.
A fluid challenge may continue until the goal is reached as long as the safety limit is
not reached first.

85. CONGESTIVE HEART FAILURE
Oedema in CCF is due to water and salt retention (water retention is more than
salt leads to hyponatremia)
Oral route always preferred – provides better nutrition and salt restriction
DON’T
Don’t correct hyponatremia with salt supplementation- because it is dilutional
Don’t treat hyponatremia with sodium rich fluids - treat with ionotropes
Don’t chase urine output – diuretic induced
DO’S
Give less fluid
Restrict sodium
Correct potassim deficit induced by diuretic – oral route safer than IV fluid

86. ARF
General principles of Fluid and electrolyte management
Fluid restriction in oedematous and oliguric patients
Fluid intake = urine output + 500ml/day
Salt restriction – 2 to 3 gm per day
Avoid hyperkalemia
 Acute renal failure (ARF) – Fluid management as per presentation
1. Prerenal azotemia
 In oliguric patients who are not volume overload and prerenal azotemia
is likely, fluid challenge is appropriate
 500-1000ml of NS over 30-60 min may results in increased urine flow ,
if no response add Frusemid
 I V fluid in hypotensive state is NS

87. 2. Non oliguric ARF
 Due to septicemia, aminoglycosides, acute interstitial nephritis
 Carry risk of hyperkalemia and acidosis - K⁺ intake should be restricted
3. OligiricARF
 Due to acute tubular necrosis usually last for 1-3 week
 Urine output < 400 ml/day or < 0.5 ml/kg/hr
 Fluid, salt and K are restricted
 If patient needs preferred I V fluid is 5% dextrose or 10% dextrose
4. Diuretic phase ofARF
 Volume depletion and dehydration should be avoided
 Preferred I V fluid is Half strength saline (0.45%) with K⁺
requirement
as per

88. HEPATIC FAILURE
ASCITIES IN CIRRHOSIS OF LIVER
Plasma volume expansion during paracentesis by colloids like albumin, plasma
proteins, blood transfusion prevents hypotension and permits large volume
paracentesis
6-8 gm of albumin for per litre of ascitic fluid removed
FFP for coagulation disorder and whole blood for anaemia
HEPATIC ENCEPHALOPATHY
Preferred fluid → 10% dextrose, 20% dextrose and DNS to prevent hypoglycemia
Avoid
5% dextrose - hypotonic fluid aggravate cerebral edema
Isolyte-G - contains ammonium chloride which precipitate hepatic precoma
 RL – contains lactate which gets converted into bicarbonate by liver →
alkalosis If lactate metabolism is impaired leads to lactic acidosis

89. BURNS
• Extensive burns causes copious fluid loss from the circulation combined with
particular sensitivity to the effects of excess fluid administration.
• Local impairment of endothelial barrier function loss of oncotically active plasma
constituents increased capillary filtration into the interstitial compartment and
evaporative transcutaneous fluid loss due to loss of skin integrity.
• Fluid administration is based on formulas such as the Parkland formula or the Muir
and Barclay versions.
• Fluids are down-titration of administered fluid volumes if urine output is adequate
(0.5 to 1 mL/kg/hr)

90. FLUID THERAPY IN VOMITING
vomiting and nasogastric aspiration commonly encountered problems are
Hypovolemia –dehydration due to loss of fluid
Hypokalemia ↓
Loss in vomitus
Loss Na⁺ in gastric juice → ↑aldosteron → Na⁺ reabsorption and K excretion
Metabolic alkalosis
Upper GI loss of H⁺
Hypovolemia → ↑reabsorption of HCO₃ in proximal tubules
High aldosteron will secrete H⁺ ion ( insterad of K⁺ ) →Aciduria → metbolic
alkolosis
 Loss chloride lead increased HCO₃ reabsorption
Hypochloremia – loss in GIT → ↑ renal absorption of HCO₃ → alkalosis

91. Isotonic saline
Corrects fluid deficit → ↑ECF → ↓HCO3 absorption → Correction M.Alkalosis
Correction of volume and Na⁺ → ↓ aldosteron → ↓ K⁺ and H ⁺secretion →
Correction of hypokalemia and alkalosis
Corrects Hypochloremia → fovours HCO₃ secretion → correction of
M.alkalosis
Isotonic saline corrects all biochemical abnormalities except K⁺ deficit
Isolyte-G
Is the specific fluid for upper replacement of GI loss, it corrects H⁺, Cl⁺, K⁺ and
Na⁺

92. TRAUMA
• Large volumes of IV crystalloids or colloids in early resuscitation will cause
hemodilution and dilute clotting factors, and saline-based fluids may aggravate the
acidosis associated with major blood loss
• Rather, packed RBCs (PBRCs), clotting factors (e.g., fresh frozen plasma [FFP])
and platelets should be replaced early
• Studies show that “high” ratios of FFP to PRBC (e.g., 1:1 to 1:2) are associated
with the best outcomes in massive transfusion.

93. NEUROSURGICAL CASES
• Aim is to keep patient normovolemic and normo or slightly hyperosmolar with
normal sodium balance
• Safe I V fluids- NS, 5% albumin, 6% hetastarch are iso to hyperosmotic, so they
have minor effect on brain’s water content or ICP
• Cautious use – osmolarity of RL is 274 mOsm/L and 5%dextrose is 278 mOsm/L.
Both are hypotonic can cause cerebral edema and raised ICP
• Dextrose produces hyperglycemia and anaerobic oxidation of glucose produces
lactic acid which further damages brain
• Mannitol is the mainstay of therapy for raise ICP – Mannitol is impermeable to BBB
therefore drains water out of edenatous brain into plasma
• NS has 308 mOsm/L osmolality is ideal and cheap

94. CRYSTALLOIDS COLLOIDS
Aqueous solution of low molecular weight ions
with or without glucose
High molecular weight substances similar to
plasma proteins
Readily pass through semi permeable membrane –
extravascular space expanders
Do not cross capillary membrane – intravascular
space expanders.
Intravascular t1/2 – 20-30 min 2-8 hrs
Reduces colloid oncotic pressure Maintain colloid oncotic pressure
Poor capillary perfusion Good
Risk of overhydration  tissue edema Insignificant.
No anaplylactic reactions More
In expensive Expensive
Readily available, well tolerated by patients Not so

95. COLLOID–CRYSTALLOID CONUNDRUM
• There is a longstanding debate concerning the type of fluid that is most appropriate for
volume resuscitation, and each type of fluid has its loyalists who passionately defend
the merits of their chosen fluid.
• Crystalloid fluids were popularised for volume resuscitation for their ability to expand
interstitial volume than plasma volume.
• But recently, importance was given to promote cardiac output , systemic oxygen
delivery as the primary focus of volume resuscitation .Here ,colloids have proven
superior.

96. • Despite the superiority, crystalloids remain popular choice for volume resuscitation
because of
• Lower cost of crystalloid fluid.
• Lack of survival benefit with colloid resuscitation.
• The problem with crystalloid resuscitation – promotes edema ,positive fluid balance
 increasing morbidity and mortality.
• No clear consensus exists on which intravenously administered fluid is associated with
the best clinical outcomes in the perioperative setting.
• Comparisons of “balanced” with “unbalanced” and “crystalloid” with “colloid” fluids
are being studied in many clinical settings but definitive conclusions are often lacking.
• The approach to fluid and electrolyte management may need adapting to numerous
patient and surgical factors.
• Hence ,a problem based approach is necessary .

97. A problem-based approach
• The colloid-crystalloid controversy is fueled by the premise that one type of fluid is optimal
in all cases of hypovolemia.
• This seems unreasonable , since no single resuscitation fluid will perform optimally in all
conditions associated with hypovolemia.
• Example:
• life threatening hypovolemia due to blood loss – blood products / albumin
• Hypovolemia due to dehydration – crystalloid resuscitation
• Tailoring the type of resuscitation fluid to the specific cause and severity of hypovolemia is
a more reasoned approach than using the same type of fluid for all cases of hypovolemia.

98. Sir Henry Tizard quoted-
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99. REFERENCES
• Miller’s Anaesthesia- 8th edition.
• The ICU book – Paul marino - 4th edition.
• Morgan and Mikhail's Clinical Anaesthesiology - 5th Edition
• Stoelting's Pharmacology and Physiology in Anaesthetic Practice - 5th Edition.
• Practical guidelines on fluid therapy – Dr. sanjay Pandya – 2nd edition.
• Toscani et al. Critical Care (2017) 21:207 DOI 10.1186/s13054-017-1796-9What is the impact of the fluid
challenge technique on diagnosis of fluid responsiveness? A systematic review and meta-
analysis Laura Toscani, Hollmann D. Aya, Dimitra Antonakaki, Davide Bastoni, Ximena Watson, Nish Arulkumaran, Andrew
Rhodes and Maurizio Cecconi
• Indian Journal of Anaesthesia 2009; 53 (5):592-607Are All Colloids Same? How to Select the
Right Colloid?Sukanya Mitra1, Purva Khandelwal2
• British Journal of Anaesthesia : Pendulum swings again: crystalloid or colloid fluid therapy 113
(3): 335–7 (2014) Advance Access publication 14 March 2014 . doi:10.1093/bja/aeu015 M. C. Kelleher1* and D. J. Buggy1,21 Department of
Anaesthesia, Mater Misericordiae University Hospital&School of Medicine&Medical Science, University College Dublin, Ireland 2 Outcomes
Research Consortium, Cleveland Clinic, OH, USA.
• Honore et al. Ann. Intensive Care (2016) 6:120 DOI 10.1186/s13613-016-0227-4 Normal saline as
resuscitation fluid in critically ill patients: not dead yet! Patrick M. Honore*, Rita Jacobs and Herbert D.
Spapen

101. Thank you