colloids with their properties and their benefits and disadvantages . indications for colloids. types of colloids and their effect on volume expansio.various studies done for colloids. body fluid compartments and distribution of total body water.
An excellent tool to treat refractory hypoxia. Target audience are ICU junior physicians and Respiratory Therapists. It will take away the fear of "What is APRV?" from your hearts and you will feel ready to give it a try.
colloids with their properties and their benefits and disadvantages . indications for colloids. types of colloids and their effect on volume expansio.various studies done for colloids. body fluid compartments and distribution of total body water.
An excellent tool to treat refractory hypoxia. Target audience are ICU junior physicians and Respiratory Therapists. It will take away the fear of "What is APRV?" from your hearts and you will feel ready to give it a try.
Physiology of water balance and HypernatremiaAbdullah Ansari
Distribution of body water
Functions of body water
Daily water balance
Plasma Osmolality
Water metabolism
Vasopressin
Stimuli for vasopressin release
Thirst
Hypernatremia
Approach to Hypernatremia
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
CDSCO and Phamacovigilance {Regulatory body in India}NEHA GUPTA
The Central Drugs Standard Control Organization (CDSCO) is India's national regulatory body for pharmaceuticals and medical devices. Operating under the Directorate General of Health Services, Ministry of Health & Family Welfare, Government of India, the CDSCO is responsible for approving new drugs, conducting clinical trials, setting standards for drugs, controlling the quality of imported drugs, and coordinating the activities of State Drug Control Organizations by providing expert advice.
Pharmacovigilance, on the other hand, is the science and activities related to the detection, assessment, understanding, and prevention of adverse effects or any other drug-related problems. The primary aim of pharmacovigilance is to ensure the safety and efficacy of medicines, thereby protecting public health.
In India, pharmacovigilance activities are monitored by the Pharmacovigilance Programme of India (PvPI), which works closely with CDSCO to collect, analyze, and act upon data regarding adverse drug reactions (ADRs). Together, they play a critical role in ensuring that the benefits of drugs outweigh their risks, maintaining high standards of patient safety, and promoting the rational use of medicines.
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
2. Part 1
• Fluid compartments and distribution
• Crystalloids
• Colloids
3. Part 2
• Clinical fluid and electrolyte management
• Appropriate fluid selection
• Goal directed fluid therapy
• Intra operative fluid management
• Fluid therapy in specific situations
4. • Water makes up approximately 60% of total body weight in the average adult, varying
with age, gender, and body composition.
• Adipose tissue contains little water compared with other tissues,
• marked variability in total body water (TBW)
• TBW - Lean (75%) and obese (45%) individuals.
• Variation in adipose tissue - differences in TBW between adult males and females
• these differences are reduced in old age as adipose tissue is reduced.
10. TBW is divided between sequestered and functional Fluid compartments
Division between intracellular fluid (ICF) and extracellular Fluid (ECF).
the ratio between ICF and functional ECF is approximately 2:1
(ICF 55% of body weight to ECF 27.5% of body weight).
11.
12.
13. • Lymphatic fluid, fluid in intercellular spaces
INTERSTITIAL FLUID
• Plasma volume including fluid in subglycocalyx
INTRAVASCULAR FLUID
• (GI) tract fluid, bile, urine, csf, aqueous humor, joint fluid, and pleural,
peritoneal, pericardial fluid
TRANSCELLULAR FLUID
• substantial proportion of TBW
• but not part of the functional ECF because of slow kinetics of water
distribution between this and other compartments
FLUID IN BONE AND DENSE CONNECTIVE
TISSUE
17. • Diffusion. Diffusion is the process by which
solute particles fill the available solvent
volume by motion from areas of high to low
concentration.
• Fick’s law of diffusion
18. osmosis
• If a semipermeable membrane (one that is permeable to
water but not a solute) separates pure water from water in
which solute is dissolved, water molecules will diffuse across
the membrane into the region of higher solute
concentration.
• The hydrostatic pressure required to resist the movement of
solvent molecules in this way is osmotic pressure.
• depends on the number rather than the type of osmotically
active particles in a solution, which may be complete
molecules or dissociated ions.
• Osmotic pressure in an ideal solution is affected by
temperature and volume:
21. 0ncotic Pressure
Component of total osmotic pressure that is due to the colloids—
• large-molecular-weight particles, predominantly proteins (albumin, globulins,
fibrinogen).
• Of the total plasma osmotic pressure of 5545 mm Hg, 25 to 28 mm Hg is due to plasma
oncotic pressure.
• The negative charge on proteins has the net effect of retaining a small excess of Na+ ions
within the plasma (the Gibbs-Donnan effect)
• increases the oncotic pressure above what would be predicted by calculations based
purely on protein concentration.
• albumin is responsible for 65% to 75% of plasma Oncotic pressure.
24. • This is the behaviour of charged particles in solutions separated by a
semipermeable membrane, which doesn't allow some of the particles
to pass.
• The equilibrium that results is a balance between the electrostatic
forces and the osmotic forces affecting these ions.
• The negative charge on proteins has the net effect of retaining a small
excess of Na+ ions within the plasma (the Gibbs-Donnan effect)
28. Osmolality
• Molality is the number of moles (each containing 6
×10 (23) particles of a specific substance present in 1
kg of solvent
• Normal body osmolality is 285 to 290 mOsm/kg
• Same in intracellular and extracellular compartments
• because of the free movement of water between
compartments that consequently prevents the
development of any osmotic gradients.
29. Osmolarity
• number of osmoles of solute per liter
of solution
• affected by temperature changes as a
result of the volume expanding effect
of increasing temperature.
30. Tonicity
• effective osmolality of a solution with respect to a particular semipermeable membrane and takes into
account solutes that do not exert an in vivo OSMOTIC EFFECT
• Na and Cl do not cross cell membranes freely and therefore exert
an effective osmotic force across these membranes
• whereas urea freely diffuses across cell membranes and
therefore does not exert an osmotic effect
• Glucose – ineffective osmole
• Tonicity is Sensed by the hypothalamic osmoreceptors.
• It can be estimated by subtracting urea and glucose concentration from measured osmolality
31.
32. VASCULAR ENDOTHELIUM
• Barrier function maintains intravascular volume.
• Fluid handling at capillary level.
• Endothelial glycocalyx – important semipermeable layer contributing
to barrier function
• SGL – Subglycocalyceal layer – contain protein poor fluid
• Also included under intravascular compartment
• Containing 700 – 1000ml
36. Starling's principle of transvascular fluid dynamics
• Starling, in 1896, published a paper on the absorption of fluids from
the connective tissue spaces
• basis of his work were a series of experiments injecting serum or
saline solution into the hindlimb of a dog, to track the movement of
extravascular fluid
37. • Starling deduced that the capillaries and post-capillary venules
behave as semi-permeable membranes absorbing fluid from the
interstitial space.
• Thereafter, the true "classical model" of Starling's Principle finally
took its modern form in the hands of Krooh, Landis and Turner
(1931).
41. Starling's Principle revised for the 21st century
• In 2004, Adamson and colleagues revealed that the effect of πis on
transvascular fluid exchange is substantially less than what one might
predict from the classical Starling model. This discovery had
prompted a 2010 revision of the Staring model by Levick and Michel.
• It is now established that non-fenestrated capillaries normally filter
fluid to the ISF throughout their length. Absorption through venous
capillaries and venules does not occur. πcopposes, but does not
reverse, filtration. Most of the filtered fluid returns to the circulation
as lymph
42. • Levick and Michel ”the small pore system of the transvascular semi-
permeable membrane” is the endothelial glycocalyx layer (EGL).
• It covers the endothelial intercellular clefts, separating plasma from a
‘protected region’ of the subglycocalyx space which is almost protein-
free.
• Subglycocalyx COP (πsg) replaces πis as a determinant of transcapillary
flow (Jv)
43.
44. From indocyanine green dilution studies,
the human EGL volume was estimated to be about 700 ml
and presuming that the endothelial surface area approximates 350 m,
an average EGL thickness of about 2 μm was suggested
45. Hydostatic pressure favours movement
of water out of capillaries
Water maybe exchanged between the glycocalyx
& the plasma in response to changes in
plasma oncotic pressure
Ultrafiltered fluid returns to
the circulation as lymph
Subglycocalyceal space is relatively protein free
46.
47. Jv = Kf ([Pc − Pi] − σ [πc − πsg])
Jv transcapillary flow
Kf filtration coefficient
Pc capillary hydrostatic pressure
Pi interstitial hydrostatic pressure
σ is the reflection coefficient
(the degree to which the tendency of a macromolecule
to cross the endothelial barrier is resisted)
πc capillary oncotic pressure
πsg subglycocalyx oncotic pressure
52. Physiologic Control of Overall Fluid Balance
• 60% of daily water loss is through urinary excretion
• proportion is less when sweating and insensible losses are increased
• Perioperative challenges??
1.reduced oral fluid intake
2.increased lower GI tract loss as a result of bowel preparation,
3.blood loss,
4.IV infusion of fluids
• cardiovascular
• renal
• neuroendocrine mechanisms
maintain fluid volume homeostasis
53. • TBW volume is controlled by a system of
1. sensors - hypothalamic osmoreceptors, baroreceptors
2. central control - hypothalamus
3. Effectors
sensors
• hypothalamic osmoreceptors - changes in ECF tonicity,
• low-pressure baroreceptors in the large veins and right atrium - central
venous pressure,
• high-pressure baroreceptors in the carotid sinus , aortic arch - changes in
intravascular volume are sufficient to affect arterial blood pressure.
54. • integrated within the hypothalamus,
• triggers the effector mechanisms
1. to either increase water intake by thirst
2. modulate output via antidiuretic hormone (ADH, arginine
vasopressin) secretion.
55. • Thirst and ADH release may be triggered by
1) increased plasma tonicity
2) hypovolemia
3) hypotension
4) angiotensin II
5) stress (including surgery and trauma) drugs(e.g., barbiturates).
HYPOVOLEMIA
HYPOTENSION
ADH SALT WATER
RETENTION
58. ADH
• produced in the hypothalamus
• Released from the posterior pituitary,
• acts on the principal cells of the renal collecting ducts, which in the
absence of ADH
are relatively impermeable to water
59. • ADH combines with the vasopressin 2 (V2) receptors
on the basolateral membrane
of the cells, triggering cyclic adenosine
monophosphate (cAMP)-mediated insertion of
aquaporin 2 water channels into the apical
membrane.
• results in water reabsorption down its osmotic
gradient and formation of low volumes of
concentrated urine.
60.
61.
62. Acute Disturbances in Circulating Volume
• Compensatory mechanisms over minutes to hours in an attempt to
correct the acute abnormality.
• Minimizing the change in effective blood volume
• 1. venoconstriction
2. mobilization of venous reservoirs
3. autotransfusion from ISF to plasma
4. reduced urine production
5. maintenance of cardiac output and arterial pressure
{tachycardia, increased inotropy, and vasoconstriction}
63. • The sensor organs for the acute change are the low-pressure and
high-pressure baroreceptors
• increased sympathetic outflow.
• Renal vasoconstriction leads to a reduced volume of filtrate and
activates the renin-angiotensin-aldosterone (RAA) axis.
64. Overall result
1. increased renal salt and water retention
2. increased peripheral vascular resistance
3. increased cardiac output.
• In the absence of ongoing loss, the delayed responses to major blood loss
restore plasma
1. volume within 12 to 72 hours
2. increase hepatic plasma protein synthesis
3. restore RBC levels by erythropoiesis
within 4 to 8 weeks.
65. • the infusion of fluid to a normovolemic
healthy adult leads
• initial rise in
1. venous pressure
2. arterial pressure
3. cardiac output.
• At tissue level, autoregulatory responses lead to arteriolar
vasoconstriction to maintain constant blood flow in the face of
increased perfusion pressure.
66. • proportion of infused fluid lost
1. Capillary filtration
Low-pressure baroreceptor stimulation leads to decrease in pituitary
ADH secretion, allowing
2.diuresis
• atrial stretch leads to atrial natriuretic peptide (ANP) release favoring
3.natriuresis
67. • pressure natriuresis and pressure diuresis
• pressure-volume control mechanism
• key mechanism for the long-term maintenance of normal blood
volume.
68. • arterial blood pressure is only slowly restored by cardiovascular
reflexes after acute hypervolemia.
• It may take several days for a 20 mL/kg dose of isotonic salt solution
to be fully excreted
74. Fluid pharmacology…???
Should be considered as drugs with
• Specific indications
• Cautions
• Dose ranges
• side effects
• Lack of knowledge of the composition among clinicians are linked to
poor prescribing practices
75.
76. Crystalloids
• Crystalloids are solutions of electrolytes in
water.
• Crystalloids containing a range of electrolytes
also found in plasma and a buffer such as
lactate or acetate may be referred to as
balanced solutions.
Crystalloids are indicated for
• Replacement of free water
• Replacement of electrolytes
• Volume expansion.
77. Conventional CONCEPT
• You are giving crystalloid/colloid iv
• water will follow down osmotic gradients
• infused electrolytes will distribute freely throughout the ECF
• Infused crystalloid has been thought to distribute evenly throughout
the extracellular compartments as a result of capillary filtration
• Only 20% remaining in the intravascular compartment. In other
words, approximately one fourth or one fifth of the original volume is
within the circulating blood volume
• whereas colloids were presumed to initially remain largely within the
intravascular volume.
78.
79.
80. Microvascular fluid handling – newer concept
• studies of the effects of fluids on blood volume are based on red
blood cell (RBC) dilution and changes in the hematocrit and do not
take into account the influence of the SGL volume, from which RBCs
are excluded.
• Colloids are excluded from the SGL , they remain in the plasma
volume they will have a diluting effect on the hematocrit and appear
to remain within the circulating volume.
81. • Crystalloids initially distribute throughout the plasma and SGL
volumes.
• As a result, their RBC dilutional effects are less than those of colloids.
• This has previously been interpreted as crystalloid leaving the
circulating compartment and entering the ISF.
• however, a proportion of the infused crystalloid will remain in the
blood volume within the SGL
• The clearance of crystalloid from intravascular compartment was also
found to be slow under anaesthesia
82. • So, in low perfusion states as in resuscitation, crystalloid/colloid ratio
of 1.5:1 is now predicted as opposed to previously predicted 4:1 ratio
• In other words, in such situations, the amount of crystalloids to
produce a desired volume expansion is nearly the same as that of
colloids
• isotonic crystalloids may have a larger intravascular volume expanding
effect than what was thought earlier
83. • Tissue edema may increase in compliant tissues such
as the lung, gut, and soft tissues, particularly when
crystalloid solutions are infused into normovolemic
subjects.
• Large-volume crystalloid infusion also may be
associated with a hypercoagulable state caused by
dilution of circulating anticoagulant factors
84. 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
85. General characteristics of Crystalloid
all the compartments i.e intracellular and
• Contains water and electrolytes
• Non ionic solutions expands
extracellular space
• Sodium cannot gain access into the intracellular space. Hence all sodium will
remain in the extracellular space thus expanding it
88. Saline solutions
0.9% Sodium Chloride.
• most commonly administered crystalloid
• 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
• Osmolarity slightly higher than that of plasma
• the osmolality is 285 mOsm/kg, very similar to that of plasma.
• This discrepancy reflects the nonideal behavior of solutions
89. The normality of a solution is the gram equivalent
weight of a solute per liter of solution
• 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 solution’ 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
90. • Composition
Na-154 meq/l
Cl- 154 meq/l
NaCl 0.9gm/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.
91. 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
825ml
92. 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)
93. 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
94. • 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
95.
96. Infusion of 0.9% Normal Saline leads to
• an increase in ECF volume,
• dilutional decrease in hematocrit and albumin,
• increase in Cl− and Na+ concentrations,
• decrease in plasma HCO3
• The expansion of the ECF is more persistent
than with balanced crystalloid solutions
• although both fluids induce diuresis, this has a later onset and is less
extensive with isotonic saline
• Infusion of saline leads to a hyperchloremic metabolic acidosis and reduced
renal perfusion
97. • increased incidence of kidney injury and requirement for renal
replacement therapy are seen when compared with the use of lower
Cl− solutions.
• the large-volume (50 mL/kg) infusion of 0.9% NaCl led to abdominal
discomfort, nausea, and vomiting.
98. • volume of saline administered perioperatively should be limited
unless there are compelling indications like.
1. cerebral edema
2. gastric outlet obstruction
99. 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
100. 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
102. Hypertonic Saline.
• Solutions of 1.8%, 3%, and 7.5% NaCl are available.
• PHARMACOLOGICAL PROPERTIES
Plasma volume expansion:
1. The hypertonic nature of these solutions draws water
out of the intracellular compartment and into the
extracellular (including plasma volume)
achieve plasma volume expansion while minimizing the
volume of fluid administered
103. 2. Correction of hypoosmolar hyponatremia
3. Treatment of increased intracranial pressure
[Hypertonic saline may be superior to mannitol]
4. 7.5% - endothelial injury used as sclerosant
104. Balanced crystalloid solutions
• Balanced crystalloids are fluids formulated to have a neutral pH and concentration of
electrolytes
• similar to that of human plasma
• Crystalloids containing a range of electrolytes also found in plasma and a buffer such as
lactate or acetate may be referred to as balanced solutions.
• Ringer lactate
• Hartmann solution
• Plasmolyte solution
105. 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
106. • Have lower overall osmolarity than 0.9% NaCl, with a lower Na+ concentration
and much lower Cl− concentration.
• reduction in anionic content is compensated for by the addition of stable organic
anionic buffers such as lactate, gluconate, or acetate
• The measured osmolality of balanced solutions (265 mOsm/kg) is slightly lower
than that of plasma, and they are therefore mildly hypotonic.
• Fluid compartment distribution of balanced solutions is similar to that of other
crystalloids
111. • The excretion of the excess water and electrolyte load with balanced
crystalloids is more rapid than with isotonic saline.
• Transient decrease in plasma tonicity after infusion, which suppresses
ADH secretion and allows diuresis in response to the increased
intravascular circulating volume.
112. • Balanced crystalloids do not reduce plasma SID ( strong ion
difference) to the same degree as NaCl solutions
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
• do not cause acidosis
• HCO3 concentration is maintained or slightly elevated.
113. • Lactated Ringer solutions contain racemic (d- and l-) lactate, although
d-lactate is only found in trace quantities in vivo.
• large doses of d-lactate may be associated with encephalopathy and
cardiac toxicity in patients with renal failure.
114. LACTATE
• hepatic metabolism
• should be avoided in severe liver failure.
ACETATE
• excess exogenous acetate - syndrome of acetate
intolerance
• experienced by patients undergoing hemodialysis with
acetate-based dialysate
• ACETATE - proinflammatory, myocardial depressant,
vasodilatory, and hypoxemia promoting.
115. 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
116. 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
118. INDICATIONS AND LIMITATIONS
Isolyte G… “The gastric replacement solution”
Vomiting /NGT induced hypochloremic hypokalemic metabolic alkalosis.
NH4 gets converted to H+ and urea in the liver.
Treatment of metabolic alkalosis.
Provides all electrolytes lost via gastric juice, corrects alkalosis,
Provides calories
The only available IVF which directly corrects metabolic alkalosis
Be cautious in : hepatic failure , renal failure , metabolic acidosis
ISOLYTE M… “The maintanence solution with D% dextrose”
Richest source of potassium (35mEq)
correction of hypokalaemia.
LIMITATIONS : Renal failure ,burns, adrenocortical insufficiency,
hyponatremia
119. ISOLYTE P:“the paediatric maintanence fluid”
Maintenance fluid for children.
Excessive water loss or inability to concentrate urine .
LIMITATIONS : hyponatremia , renal failure,
hypovolemic shock
ISOLYTE E:“the Extracellular replacement solution”
Double the concentration of potassium and acetate.
Only ivf which corrects Mg deficiency.
Treatment of diarrhoea and metabolic acidosis.
LIMITATIONS : metabolic alkalosis.
120. 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.
125. 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
126. 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
127. 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
130. 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.
131. Dextrose Solutions
• 1. As a source of free water
• infusion of 5% dextrose effectively represents administration of free
water.
• dextrose is taken up into cells in the presence
of insulin, leaving free water.
• hypotonic with respect to the cell membrane
• IF IN EXCESS dilute plasma electrolytes and
osmolality.
132. • use with care in the postoperative period
(SIADH)
• water retention, increasing risk for hyponatremia
• useful source of free water for maintenance requirement
postoperatively, particularly if combined with a low concentration of
NaCl
133. • 2. Source of metabolic substrate
• 3. coadministered with IV insulin to patients with diabetes to reduce
the risk for hypoglycemia, such as 10% dextrose
at 75 mL/hr.
134. 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.
135. 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)
136. 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
137. 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
138. 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
139. 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
140. 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
141. 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
142. 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
and in delirium
the absence of
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
147. COLLOIDS
• The term colloid is derived from Greek word “Glue”.
• These solutions are also called suspensions
Colloid is defined as large solute molecules or ultramicroscopic particles of a
homogeneous noncrystalline substance dispersed in a second substance, typically
isotonic saline, or a balanced crystalloid
These particles cannot be separated out by filtration or centrifugation
• 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
148.
149. 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
150. 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
151. • Colloid molecules above 70 kDa are too large to pass through the
endothelial glycocalyx and are excluded from the subglycocalyx layer
• initial volume of distribution same as the plasma (rather than the entire
intravascular volume)
• Colloids have a higher COP and minimize transcapillary
filtration,particularly at low capillary hydrostatic pressures.
• This maximizes their potential intravascular plasma volume expansion
effect.
• At normal or supranormal capillary pressures, hydrostatic pressure will be
increased andtranscapillary filtration will occur.
152. Colloid molecules may be lost from circulation in several ways
• filtration across capillaries
• renal filtration of smaller colloid molecules
• removal from the circulation by metabolism
Colloids have variable effective plasma half-lives
153. Colloids alter blood rheology, typically improving blood flow by
• hemodilution
• reductions in plasma viscosity
• reduction in red cell aggregation effects
Large dose of semisynthetic molecules (typically 40 to 60 g/L) –
undesired effects on the immune, coagulation, and renal systems.
Adverse effects may still occur with smaller administered doses.
155. semisynthetic colloids
• a range of molecular sizes (polydispersed)
human plasma derivatives
• more than 95% albumin molecules of a uniform size
(monodispersed).
156. Human Plasma Dervivatives
• human albumin solutions
• plasma protein fractions
• fresh frozen plasma
• Immunoglobulin solution.
theoretic risk for transmission of variant
Creutzfeldt-Jakob disease remains, associated with bovine spongiform
encephalopathy
157. 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
158.
159. 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
160.
161. 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
162. 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.
164. SEMISYNTHETIC COLLOIDS
• GELATIN
• derived from the hydrolysis of bovine collagen, with subsequent
modification by succinylation ( GELOPLASMA) – undergoes
confirmational change – negative charges - larger molecules.
• urea-linkage to form polygeline ( HAEMACCEL)
165. EXCRETION IS
PRIMARILY BY THE
RENAL ROUTE.
NEGATIVE EFFECTS HIGHEST ESTIMATED
INCIDENCE OF
SEVERE
ANAPHYLACTIC AND
ANAPHYLACTOID
REACTIONS
HIGH CA2+ CONTENT
OF HAEMACCEL IS A
CONTRAINDICATION
TO
COADMINISTRATION
OF CITRATED BLOOD
PRODUCT IN THE
SAME INFUSION SET.
NOT APPROVED BY
THE U.S. FOOD AND
DRUG
ADMINISTRATION
166. 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 of35,000.
• 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)
167. 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 Regional Anaesthesia
• Priming Of Heart Lung Machines
168.
169.
170.
171. 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:
incidence of• Anaphylactoid reactions: Gelatins are associated with higher
anaphylactoid reactions as compared to natural colloid albumin.
172. HYDROXYETHYL STARCH
• modified natural polymers of amylopectin(which is a highly branched
compound of starch) derived from maize or potato
• 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
• Substitution of hydroxyethyl radicals onto glucose units prevents rapid in vivo
hydrolysis by amylase
• 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
173. Physiochemical Properties
• Concentration: low (6%) or high (10%). Concentration
mainly influences the initial volumeeffect:
• 6% HES solutions are iso-oncotic
• 10% solutions are hyperoncotic
• Average Molecular Weight(MW):
• low (70 kDa),
• medium ( 200 kDa)
• high ( 450 - 480 kDa)
174. 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 hydroxyethyl radical.
Number of substituted glucose molecules present divided by the total number of
glucose molecules present
• Molar substitution (MS) ratio, calculated as the total number of hydroxyethyl
groups present divided by the quantity of glucose molecules.
• 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
0.5 MS means there are 5 hydroxyethyl residues in 10 glucose subunits
175. MS determines the category of HES
• hetastarches (MS 0.7)
• hexastarches (MS 0.6)
• pentastarches (MS 0.5)
• tetrastarches (MS 0.4)
176. C2/C6 hydroxyethylation ratio
• The pattern of substitution may vary
• hydroxyethylation can occur at carbon positions 2, 3, or 6 of the
glucose unit.
• The substitution type is defined by the C2/C6 hydroxyethylation ratio
• higher ratio leads to slower starch metabolism
177. • high MW (450 to 480 kDa)
• medium MW (200 kDa)
• low MW (70 kDa)
• HES solutions are very polydispersed and the MW quoted is an
average
178. • Determinants of HES kinetics of elimination.
1. degree of hydroxyethyl substitutions per glucose unit (maximum
three)
2. total number of glucose units with substitutions
179. • size of starch molecule is responsible for both
the therapeutic volume effects and adverse side
effects
• this changes when infused; smaller HES molecules
(<50 to60 kDa) are rapidly excreted and larger
molecules are hydrolyzed to form a greater number of
smaller molecules at a rate depending
• 1. degree of substitution
• 2. C2/C6 hydroxyethylation ratio.
The in vivo MW is therefore smaller and has a narrower
distribution.
180. • Renal excretion accounts for the elimination of smaller HES molecules
• medium-sized molecules being excreted in the bile and feces
• proportion of larger molecules, particularly those resistant to
hydrolysis, is taken up by the mononuclear phagocyte
(reticuloendothelial) system, where they may persist for several
weeks or more
181. • The prolonged metabolism of HES means that their plasma volume
effects typically last longer than those of gelatin or crystalloids, with
larger MW starches increasing intravascular volume by approximately
70% to 80% of the infused dose at 90 minutes.
Smaller MW starches with a low MS may have even larger volume
effects as a result of the rapid initial metabolism with the formation
of a large number of oncotically active molecules.
182.
183.
184. ADVERSE EFFECTS
• Coagulation defect –
1. dilutional effects in the circulation
2. MW-dependent reductions in vWF, factor VIII, and
clot strength
• most likely to occur with larger MW or slowly
degraded medium MW
(200 kDa/MS 0.62 or 200 kDa/MS 0.5/C2:C6 13) HES
• preparations and larger amounts of perioperative
blood loss.
185. • This clinical effect is less marked with more rapidly degraded medium
and small MW starches
• In patients with sepsis, even lower MW HES is associated with an
increased risk of bleeding
186. • Accumulation
• skin, liver, muscle, gut
• larger degree of tissue deposition is
• associated with pruritus
• Anaphylactoid Reactions
187. • Renal Dysfunction
medium to high MW are associated with
• oliguria
• increased creatinine,
• acute kidney injury in critically ill patients with preexisting renal
impairment
188.
189.
190.
191. 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.
192. 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 , factorVIII
• 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
193. 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).
194. • large MW dextrans produced undergo acid hydrolysis to yield smaller MW
molecules,
which are then separated by fractionation to produce a solution with a
restricted range of MWs.
• dextrans have an average MW of 40 kDa or 70 kDa.
• Polydispersal - a proportion of smaller MW molecules are present that are
rapidly filtered at the glomerulus
• 70% of a dextran dose is renally excreted within 24 hours.
• Higher MW molecules are excreted into the GI tract or taken up into the
mononuclear phagocyte system, where they are degraded by endogenous
dextranases
195. 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.
196. • plasma volume effect similar to that of starches, with a duration of 6
to 12 hours.
• dextran 40 may be used in microvascular surgery, where its dilutional
effects on blood viscosity and anticoagulant favor flow in the
microcirculation.
197. • Antithrombotic effect:
Marked in lower MW dextrans
• red cell coating
• inhibition of aggregation, factor VIIIc and vWF
• Reductions and impaired activity of factor VIII.
• Platelet aggregation is also inhibited.
Impaired hemostasis and increased perioperative blood loss.
• Blood cross-matching: Dextrans coat the erythrocyte
• cell membrane and may interfere with blood type
• cross-matching.
198. • Anaphylactoid reactions:
intermediate risk for serious anaphylactic and anaphylactoid reactions
• Renal dysfunction:
resulting from osmotic nephrosis is recognized after low-MW dextran
infusion.
199. 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.
200. 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.
201. First generation colloids
• 1st dextran was introduced to market 1944.
• Not used nowadays due to allergic reaction , R.F. & interfere blood
grouping
203. Third generation colloids
• 1st clinical use during Vietnam war 1959-1975.
• 1st synthetic colloids with globular configuration similar to albumin.
• Derived from Maize & potato starch.
• HES much lower viscosity than others but not reach to albumin.
• Types :
1- Heta-starch: MW 450000 - Hesteril.
2- Penta-starch : MW 200000.
3- Tetra-starch : MW 130000- Voluven.
204. 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