IV FLUID MANAGEMENT/ FLUID THERAPY

IV FLUID ANAGEMENT

1. FLUID THERAPY Presenter : Dr Ashutosh 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 Co lloid 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.”

6. 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

7. CRYSTALLOIDS

8. CRYSTALLOIDS Crystalloid are electrolyte solutions with small molecules that can diffuse freely from intravascular to interstitial fluid compartments 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

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

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

11. 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

12. 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

13. 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.

14. 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)

15. 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.

16. 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

17. 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

18. 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 prerenal ARF Irrigation for washing of body fluids Vehicle for certain drugs

19. 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

20. 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

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

22. 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

23. 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

24. 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

25. 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 HCO 3- __ 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

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

27. 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

28. 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

29. 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.

30. 5 % DEXTROSE Composition : Glucose 50 gms /L + free water Pharmacological Basis Corrects Dehydration And 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. A proportion of dextrose load contributes to lactate formation – 5% in healthy subjects 85% in critically ill patients ----hence not the preferred fluid.

31. 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 )

32. Limitations of 5D Neurosurgical procedures - can aggravate Cerebral oedema and increase ICT 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 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. Hyponatremia & water intoxication - 5%D worsens both conditions

33. 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

34. DEXTROSE SALINE (DNS) Composition N a- 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

35. 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

36. 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 Fluid therapy in paediatric – In paediatric group ratio of requirement of water : NaCl is double as compared to adults Treatment of severe hypernatremia – It corrects hypernatremia gently, it avoids cerebral edema Maintenance fluid therapy and in early post operative period. Limitations Hyponatremia Severe dehydration where larger salt replacement is needed

37. 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

38. 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 and in delirium tremens Avoided in patients with diabetes unless there is hypoglycemia. Rapid infusion of 25D can cause glycosuria . Hence in the absence of hypoglycemia it should be infused slowly over 45 - 60 min

39. HYPEROSMOLAR FLUIDS MANNITOL HYPERTONIC SALINE

40. 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

41. 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

42. HYPERTONIC SALINE Available as 1.8%, 3 % , 5%, and 7.5% % Solution of NaCl gm/L Na ( mEq /L) Cl ( mEq /L) 1.8% 18 308 308 3% 30 573 573 5% 50 855 855 7.5% 75 1283 1283

43. PHARMACOLOGICAL PROPERTIES 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

44. 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

45. 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.

46. 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.

47. 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.

48. COLLOIDS

49. 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

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

51. 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

52. 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

53. 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

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

55. 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

56. 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

57. 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

58. Disadvantages 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.

59. 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 )

60. 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- 145 mmol /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 Regional Anaesthesia Priming Of Heart Lung Machines

61. 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.

62. 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

63. 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 )

64. 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 (0.7), hexastarch (MS 0.6), pentastarch (MS 0.5), and tetrastarch (MS 0.4 )

65. Indications Stabilization of systemic haemodynamics 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.

66. 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

67. 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 ).

68. 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.

69. 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.

70. 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 prevent AR F 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.

71. COLLOID ALBUMIN HETASTARCH TETRASTARCH COST EXPENSIVE CHEAP EXPENSIVE USE LONG TERM SHORT TERM ANY PERIOPERATIVE COAGULATION NO INCREASED BLEEDING INCREASED BLEEDING NO INCREASED BLEEDING RENAL TRANSPLANTATION 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

72. FLUIDS IN SPECIFIC CONDITIONS

73. 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

74. 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 Severe Anaemia However with blood transfusion haematocrite should not be raised over 35% - increase in blood viscosity lead to stasis

75. 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.

76. 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 of AKI.

77. 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. A more 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 with ARDS.

78. 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 .

79. 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’. T he 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.

80. A 4-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.

81. 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.

82. 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

83. 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 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

84. Non oliguric ARF Due to septicemia , aminoglycosides , acute interstitial nephritis Carry risk of hyperkalemia and acidosis - K⁺ intake should be restricted Oligiric ARF 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 Diuretic phase of ARF Volume depletion and dehydration should be avoided Preferred I V fluid is Half strength saline (0.45%) with K⁺ as per requirement

85. 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

86. 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 )

87. 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

88. 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⁺

89. 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.

90. 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

91. 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 t 1/2 – 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

92. 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.

93. Despite the superiority, crystalloids remain popular choice for volume resuscitation because of Lower cost of crystalloid fluid. L ack 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 .

94. 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.

95. Sir Henry Tizard quoted- “ The secret to selecting appropriate resuscitation fluid is to ask the question – what is the cause and severity of hypovolemia ?” Sir Henry Tizard quoted- “ The secret to selecting appropriate resuscitation fluid is to ask the question – what is the cause and severity of hypovolemia?”

96. REFERENCES Miller’s Anaesthesia- 8 th edition. The ICU book – Paul marino - 4 th edition. Morgan and Mikhail's Clinical Anaesthesiology - 5 th Edition Stoelting's Pharmacology and Physiology in Anaesthetic Practice - 5 th Edition. Practical guidelines on fluid therapy – Dr. sanjay Pandya – 2 nd edition. Toscani et al. Critical Care ( 2017) 21:207 DOI 10.1186/s13054-017-1796-9 What 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 Mitra 1 , Purva Khandelwal 2 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

97. Thank you