Transcript No Slide Title

NUTRITIONAL SUPPORT IN
CRITICALLY ILL
Prof. Mehdi Hasan Mumtaz
PRINCIPAL
Support for those who



Should not eat.
Will not eat.
Can not eat.
AIMS





Detection and correction of pre-existing
malnutrition.
Prevention of progressive protein energy
malnutrition.
Optimization of metabolic rate.
Reduction of morbidity.
Reduction of time to convalescence.
NUTRITIONAL ASSESSMENT



Dietary history.
Clinical examination.
Lab. Investigations.
–
–
–
–
Hypoalbuminaemia<35G/L.
Lymphocytopenia<1500/mm3.
Serum transferase<1.5G/L.
Cell mediated immunity –ve.
NUTRITIONAL ASSESSMENT



Changes in body mass.
Skin fold measurements.
Sophisticated techniques.
–
–
–
–
Neutron activation analysis.
Dual X-ray absorptiometry.
MRI.
Bioimpedance methods.
NUTRITIONAL REQUIREMENT




Nitrogen loss
Urine urea
Protein loss
Plasma urea
Nitrogen loss by pyrochemilumiscence.
Portable calorimetery (bedside).
–
–
–
–
Gas leak.
FIO2.
Water vapours.
Steady state achievement
NUTRITIONAL REQUIREMENT

Indirect calorimetry.
–
–
–
–
–

Modification.
Fever.
Sedation.
Neuromuscular paralysis.
Dialysis.
Routine practice.
– 30-35Kcal/kg body wt/day.
– 1.2-2G protein/kg body wt/day.


Electrolyte replacement.
Vitamins & trace element replacement.
PROBLEMS limiting ability to meet nutritional requirements
in critically ill patients such as:
Diuretics
Restricted fluid intake
Haemofiltration
Glucose intolerance
Good control
Delayed gastric emptying
Reduced feed absorption
Parenteral
Diarrhea
Fasting for procedures
DAILY NITROGEN LOSS

Loss in urine (24hrs-collection).
A. Urine urea (mmol)x0.0336.
B. B. Urine protein (g)x0.16.

Blood urea correction.
C. Change in plasma urea (mmol)xbody wt
(kg)x0.0168.

A + B + C (G) + Extra Real Losses.
CALCULATION OF ENERGY
REQUIREMENT
According to N2 loss
(200 Kcal/G N2
loss/day)
According to body
wt. (40-45
Kcal/kg/day)
NITROGEN LOSS
ROUGH ASSESSMENT

Moderate catabolism
10-14 G N2 loss/day
i.e. 294-420mmol UER/day.

Moderate to severe catabolism
14-24 G N2 loss/day
i.e. 420-756mmol UER/day.

Hyper catabolism states
>24 G N2 loss/day
i.e. >756mmol UER/day.
Exact Assessment
EXACT ASSESSMENT N2 LOSS
24 hrs urine urea
G x 28/60 x 6/5
Rise of urea in blood
G x 28/60 x 60% B.W
Protein urea
1GN2=6.25G of proteins
=1/6.25 x G of proteins
in urine
Total N2 Loss = 1+2+3
ROUTES OF ADMINISTRATION
Enteral




Oral F
Tube F
Gastrostomy F
Jejunostomy F
Pain
Parenteral

I/V Feeding
RARE



Allergy
Rectal
Intrausternal
Subcutaneous
Absorption
Infection
FLOW CHART
Malnutrition (Look)
(HALLMARKS)
NO
YES
NO
YES
YES
ENTERAL
(support indicated)
GI Function
NO
PARENTERAL
ENTERAL VS PARENTERAL






Better nitrogen retention.
Better weight gain.
Reduced hepatic steanosis.
Reduced GIT bleeding.
Lesser cost.
Clear physiological benefits.
– Maintain mucosal integrity.
– Maintain mucosal structure.
– Release gut trophic hormones.


Less septic complications.
Greater survival rate.
PARENTERAL NUTRITION
(un-physiological)

Bypass natural filters.

Continuous flow counter biological
rhythm.
INDICATIONS
PARENTERAL NUTRITION












Alimentary tract obstruction.
Prolonged ileus.
Enterocutaneous fistula.
Malabsorption.
Short bowel syndrome.
Inflammatory intestinal disease.
Cachexia.
Burns, severe trauma.
Adjunct to chemotherapy.
Acute renal failure.
Hepatic failure.
Hypermetabolic states.
REQUIREMENTS
BASIC

Water.
–
–
–
–
–


30-35ml/kg/day.
Extra for vomiting, diarrhoea.
150ml/1oC rise in temperature.
400ml metabolic gain.
Affected by cardiac, renal, respiratory,
hepatic disease.
Energy.
Nitrogen.
REQUIREMENTS
ADDITIONAL




Electrolytes.
Vitamins.
Trace-elements.
Additives.
ENERGY
Sources
CARBOHYDRATE
 Glucose
 Fructose
 Sorbitol
 Xylitol
 Ethanol
 Glycerol


LIPIDS
Soybean oil
emulsions
Cotton seed
emulsion
ENERGY CARBOHYDRATE

Glucose.
–
–
–
–
–
½L = 1 hr.
½L – Glycogen - 1 day.
Cal. Value – 4.3 Kcal/G.
Glycourea > 0.4 0.5 G/kg/hr.
Infusion >6-7mg/kg/min.



O2 consumption.
CO2 production.
Energy consumption with lipogenesis.
ENERGY CARBOHYDRATE

Fructose.
–
–
–
–
–
–
Insulin independent.
Rapid metabolism.
Incidence of hyperglycaemia.
Formation of glycogen.
Antiketogenic effect.
Glycosuria >1G/kg/hr.
Dehydrated
– Metabolic acidosis
Neonates
G – 6 – PO4
BARRIER
F – 6 – PO4
GLUCOSE
SORBITOL
FRUCTOSE
XYLITOL
G-6-PO4
d-XYLULOSE
G-6-PO4
6-PHOSPHOGLUCONATE
F-1:6-DPO4
RIBULOSE-5-PO4
ACETALDEHYDE
PYRUVATE
ETHANOL
NUCLEIC ACIDS
KREBS CYCLE
(PROTEIN SYNTHESIS)
CO2
H2O
ENERGY-FATS




Best choice for caloric replacement:
Caloric value.
No osmotic effect.
Urine
No loss
Faeces
SOURCES
COTTON SEE OIL



Lipomal.
Lipofundin.
Lipophysan.
SOYBEAN OIL

Intralipid
10%, 20%.
IDEAL FAT EMULSION

Size <4.

Component of utmost purity.

Should be isotonic.

Should have no effect on BP or
respiratory system.

Chronic toxicity – low.
INDICATIONS

Serious malabsorption (fistula, eneritis,
colitis).

Cachexia.

Burns.

Prolonged unconsciousness.

High calorific deficiency.
CONTRA-INDICATIONS








Hyperlipaemic states.
Nephrotic syndrome.
Renal damage.
Coagulatory disorders.
Cranial trauma.
Tetanus – other infections.
Traumatic shock.
Pregnancy.
SIDE EFFECTS
ACUTE

Circulatory.
–
–
–

Respiratory.
–
–
–





B.P Crisis.
H.R.
Shock like.
respiration.
Cyanosis.
Dyspnoea.
Pain in chest – back.
Nausea – vomiting.
Flushing of skin.
Pyrogenic reactions.
Urticaria.
SIDE EFFECTS








CHRONIC
Hyperlipaemia.
Hepato-splenomegaly.
Hepatic damage.
Icterus.
Anaemia.
haemorrhage in G.I.T.
Coagulation disorders with platelets.
Pigmentation.
SOURCES OF NITROGEN


Blood
Plasma
Catabolised to A.A first
Poor Source


Albumin
Amino-acids
EAA
AMINO-ACIDS
1GN2=25G of Muscle Tissues.
Deficiency leads to:
  Antibody formation.
  Blood regeneration and cell formation.
  synthesis of hormones & enzymes.
 Oedema.
 Coagulation.
 Muscular atrophy.
 Decubitus.
DISADVANTAGES
50-60% N2 in glycine form  NH3.
Arginine + Ornithine  K+ excretion.
 I/C – K+
Ideal A.A solution
Reactions
1:2 to 1:3 essential/
non essential
Biological adequacy
CONTRA-INDICATIONS

Severe coronary insufficiency.

K+.

Hepatic damage.

Renal insufficiency (give E.A.A. solution)

Acidosis of different origin.
ELECTROLYTES
Na+
2-2.5 mmol/kg/day.
K+
6 mmol/G N2 loss.
Ca++
0.1 mmol/kg/day.
PO-4
0.6 mmol/kg/day.
Mg+
0.1 mmol/kg/day.
Cl- acetate
Give when additional Na+, K+ given
VITAMINS
Trace elements:
Zinc, Iron, Copper, Manganese, Cobalt, Iodine, Chromium, Molyhderium &
Selenium
Zinc
Essential constituent of many enzymes e.g. carbonic anhydrase.
Iron
Essential for HB synthesis.
Copper
Important for erythrocyte maturation and lipid metabolism.
Manganese
Important for Ca++/PO4 metabolism and reproduction and growth.
Cobalt
Essential constituent of vitamins B12.
Iodine
Required for thyroxin synthesis.
Chromium
Necessary for normal glucose utilization.
Molyhderium
Component of oxidases.
Selenium
Component of glutathion peroxidase.
TRACE ELEMENT
Element
Zinc
Iron
Copper
Iodine
Manganese
Florid
Chromium
Molyhderium
Selenium
/24 h
2500-6000
500-1500
150-800
10-15
-
ADDITIVES

Insulin.

Heparin.

Anabolic steroids.
BASIC GUIDELINES





Normal N2 loss=0.2-0.24G/kg/day.
N2-energy ratio=1:200.
Energy from – glucose, fat.
N2 loss from amino acid solution.
Add.
– Electrolytes.
– Vitamins.
– Trace elements.



Spread over 24 hrs.
Energy & nitrogen given simultaneously.
Restoration of:
– Oncotic pressure.
– Hb level.
MONITORING

Biochemical.

Physiological.

Haematological.

Mechanical.

Bacteriological.

Radiological.
MONITORING





Related to kidney
Related to liver
Serum electrolytes
Acid base status
Special.
- daily.
- daily.
- twice.
- twice.
– Serum amino acid profile.
– Serum/urine zinc and Cu+2.
– Any other specific.
MONITORING
PHYSIOLOGICAL

Haemodynamics.

C.V.P.

Weight.

Fluid balance.
MONITORING
HAEMATOLOGICAL





Haemodynamics.
While cell count.
Differential count.
Serum protein.
Folate level.
MONITORING
MECHANICAL
INSEPCTION OF:
 I/V lines.
 Flow rate.
 Catheter insertion point.
 Infusion pumps.
 Monitoring equipment.
MONITORING
BACTERIOLOGICAL

Blood culture – weekly.

Viral agglutination titres.
MONITORING
RADIOLOGICAL
X-RAY CHEST
Lung Fields
CVP Catheter
NUTRITION
Acute Renal Failure











Hypercatabolic state.
Adequate calories in a low volume load.
Minimum rise in blood urea nitrogen.
Low K+ content.
Stringent sepsis control.
Concentrated glucose and lipid used.
Dialysis improve utilization.
Lipid may interfere dialysis.
Amino acid limited to 0.5G/kg/day.
Utilize endogenous urea.
Electrolyte free preparation.
NUTRITION
Hepatic Failure




Continuous use of lipids.
Calories - bulk supply – hypertonic
glucose.
Protein intake limited to 0.5G/kg/day.
Eliminate protein in hepatic coma.
NUTRITION
Respiratory Failure

Excess glucose  lipogenesis.

Excess glucose  CO2 production.

50% non-protein calories – supplied by lipid.
STRESS ON
1.
2.
Specialised Nutrition Support In
Critically Ill Patients.
Glutamine and Acute Illness.
PRESENT
&
FUTURE
SIGNIFICANCE OF GIT IN
CRITICALLY ILL
ANATOMY
&
HISTORY OF GUT
FUNCTIONS
Barrier
Transport
Endocrine
BARRIER
Permeability & Permeation
Transcellular
Paracellular
PORES
Large
(6.5nm)
Surface area of:
- 2 million cm2.
- Single tennis court.
Small
(0.4-0.7nm)
PERMEATION PATHWAYS
15%
Paracellular
(energy dependent)
85%
Transcellular
(small pores)
TIGHT JUNCTIONS
Zona Occludence)
ZO
Permeability depends:
1. Hydrodynamic radius
2. Electrical charge.
3. Functional status of ZO
Kisses + Pores
Barrier function regulation:
1. Number of kisses/cell.
2. Channels open or closed.
3. Membrane pump
FACTORS MODULATING
FUCTION OF ZO

I/C Camp Concentration.

I/C Ca+ Concentration.

Activation State Of Protein Kinase.
What is Cytoskeleton?
TRANSLOCATION
DEFINITION
CAUSES







Non Occlusive Intestinal Gangrene.
Neutropenia.
Colon Cancer.
Penumatosis Intestinals.
Necrtising Enterocolitis.
Ionizing Radiation.
Cytotoxic Drugs.
CAUSES







Cytokine Release Syndrome.
Crohns Disease.
Ulcerative Colitis.
Haemorrhagic Shock.
Severe Trauma
Burn Injury.
Leukaemia.
FACTORS
1.
2.
luminal microbial density.
Damage to eipthelium.
– Irradiation.
– Cytotoxic drugs.
– Irritants.
– Cytomegatovirus.
– Mucosal disease.
– Bowel manipulation.
– Obstruction.
– Free O2 radicals.
3.
4.
Diminished blood flow.
– Haemorrhagic shock.
– Burn.
– Inflammtory agent.
– Endotoxins.
– M. occlusion.
– Hypoxia.
– Fever.
Immunosuppressant.
– Corticosteroids in high
dosage.
– Blood transfusion.
MECHANISM
M. Cells.
Transcellular.
Ulcerations.
ALTERED PERMEABILITY
MECHANISM
Hypoperfusion
(non-occlusive
mesenteric
hypoperfusion)
ROS

Role of
Alopurinol
Corrosive
Factors
Endotoxins
NON-OCCLUSIVE
HYPOPERFUSION

Hypovolaemia.

Cardiogenic.

Septic shock.
HYPOPERFUSION
Renin Angiotensin Axis

Intense Vasoconstriction
(Splanchnic)

Hypoxic Injury – Degree
- Duration

Permeability
Large Molecules
Small Molecules

Subepithelial Oedema
Shedding Off Epithelium Top

Full Mucosal Necrosis

Disruption Of Submucosa

Disruption Of Muscular
Propria

Transmural Necrosis
ROS
Role of Allopurinal
CORROSIVE FACTORS






Hydrochloric acid.
Bile salts.
Bacteria.
Bacterial toxins.
Proteases.
Digestive enzymes.
ENDOTOXINS

Ischaemia.

Direct injury.

metabolic demand of GUT.

Alteration of micro-circulation.
MEASUREMENT OF GUT
PERMEABILITY

Isotope tests.

PEG tests.

Dual sacharide tests.
– Lactulose/Rhamnose.
– Lactulose/Mannitol.
NON MUCOSAL FACTORS

Gastric Emptying.

Intestinal Transit.

Dilution By Secretion.

Surface Area Available.

Altered Renal Clearance.
TECHNIQUE FOR MEASUREMENT
OF GUT PERMEABILITY USING LACTULOSE & L-RHAMNOSE.
Stop nasogastric feed/nil by mouth for 6 h prior to the
study.
2.
Empty bladder & urinary collecting system.
3.
Isotonic solution containing 5g oflactulose and 1g of Lrhamnose administred via the nasogastric tube.
4.
All urine collected over 5h. Total volume noted and a 20
ml sample frozen for future analysis.
5.
Concentration of sugrs in urine quantified.
6.
%recovery of each sugar calculated:
Sugar concentration x urine volume
%Recovery =------------------------------------------------------ x 100
Amount of sugar given enterally
7.
%recovery lactulose to %recovery L-rhamnose ratio
calculated. Normal range 0-0.08.
1.
IMMUNONUTRTION
(Nutritional Paharmacology)
Why Name Immunonutrition?


Lipids  -3,  -6
Aminoacids
– Arginine
– Glutamine


Ribonucleic acid
Vitamins, E,C and A
LIPIDS










Production of free radicals.
Inflammatory response.
Ulcer formation.
Hypersensitivity response.
Altered renal vascular flow.
Uterine contraction.
Incidence of atherosclerosis.
Incidence of heart attacks.
 Bleeding tendency.
Haemorrhagic strokes.
LIPIDS
-3

Immunostimulatory
– Protect against gut
origin sepsis.
– Reduce incidence of
allograft rejection
-6

Immunodepressive
VITAMINS, E,C,A

Control lipid peroxidation.

Regulate RO intermediates
(macrophages).
ARGININE
1.
Production and secretion.
–
–
–
–
–
–
–
2.
Pitintary GH.
Protaction.
IGF-1.
Glucagon.
Somatostatin.
Pancreatic polypeptide.
Nor-epinephrin.
Pre-cursor of growth factors.
– Putrescine.
– Spermine.
– Spermidine.
ARGININE
3.
4.
5.
6.
7.
8.
9.
10.
Produce NO.
Resistance.
T-cell immunity.
Wound healing.
Cancer growth.
Protein content.
Lymphocyte nitrogen & allogenic
response.
No effect on translocation.
GLUTANINE

Barrier Function.

T-cell Function.

Neutrophil Function.

Kills Translocated Bacteria.

Hospital Stay.
NUCLEOTIDES

 Resistance.

 Immune response.
EFFECT OF CRITICAL
ILLNESS ON GIT





Starvation & Bowel rest.
Metabolic stress.
Entral/Parenteral nutrition.
Sepsis.
Shock.
STARVATION
Structural

Mucosal Atrophy







Villous height.
Mucosal thickness.
Crypt dipth.
Mucosal height.
ONA, RNA
Protein contents.
Functional



Activity of
disaccharidasis.
Transport.
–
–


Glutamin
Arginine
Immunity.
IgA secretion.
GIT IMMUNOLOGIC DEFENCE




IgA.
Lymphocyte macrophages &
neutrophils.
Lymph nodes.
Kupffer cells in liver.
BOWEL REST






G.I. Mass.
Small bowel mucosal weight.
DNA content.
Protein content.
Villous height.
Enzyme activity.
Even if nitrogen balance is maintained &
on TPN
PRESENCE OF LUMINAL
NUTRIENTS NECESSARY
FOR NORMAL GUT
GROWTH & FUNCTION
ENTERAL NUTRIENTS MEDIATE
MUCOSAL TROPHISM
ENTERAL FEEDING
Direct provision of
energy & mechanical
epithelial contact
Blood vessels
Autonomic CNS
enterohormones
Pancreatic & biliary
secretions
Endocrine
effects
Dilatation &
mesenteric
blood flow
Intestinal cell proliferation & differentiation
paracrine
effects
METABOLIC STRESS
Starvation+Bowel Rest+Critical Illness, Shock, Hypovolaemia








Mesenteric blood flow.
Hypoxia.
Production of intestinal mucous.
Mucosal acidosis.
 Mucosal permeability.
Epithelial necrosis.
O2 free radicals.
Antibiotic.
–
–

Microflora.
Colonization.
Gastric acid  colonization.
Mucosal & immunologic impairment.

Passage of intraduminal microbes & toxins intocirculation.
CRITICAL ILLNESS
Hypermetabolism
+
Hypercatabolism
Nutritional support
Enteral (TEN)
To Neutralise
Disadvantages of
bowel rest
Parenteral (TPN)
Frequently utilized
- Stomach atony.
- Risk of aspiration.
- Venous access.
- Despite:
- Expensive
- Catheter sepsis
-Translocation
TEN vs TPN
Criticism  Scrutiny
TEN = Recommended.
TPN = Strong indication.
Partial TEN
TPN & IMMUNE SYSTEM

I/V lipids
– RES function.
– Bacterial clearance.

Lipid formulation -6 FA.
– Promote synthesis of Pro-inflammatory bioactive
lipids.




Secretion of IgA.
Bacterial translocation.
GUT neuro-endocrine stimulation dependent
on gut nutrient.
Glutamine – important for cellular immunity.
EFFECT OF SEPSIS
(LPS Induced Hyperpermeability)
Mucosal Hypoxia
Villous counter current
exchanging
O2 Supply.
Perfusion.
Mitochondrial oxidation

Anaerobic Metabolism

Less ATP

Cytoskeleton Integrity

Permeability
RO Metabolits

G-3P

 ATP
+
Mitochondrial
Phosphorylation

Permeability
Altered Utilization of
Substrates
Activity of glutamin

 ATP from glutamin

Cytoskeleton + ZO

Permeability
EFFECTS OF SHOCK
Effect of Ischaemia
Central Control
Local Humoral Substances
(Renin-Angiotensin)
THE CONTINUUM OF
INTESTINAL ISCHAEMIC INJURY
Normal Mucosa
Capillar Permeability
Mucosal Permeability 
Superficial Mucosal Injury
Transmucosal Injury
Transmural Injury
MECHANISM OF INTESTINAL
MUCOSAL INJURY
Ischaemic Injury
 O2 delivery.
– Reduced intestinal (mucosal) blood flow.
– Short circuiting of O2 in the villus
countercurrent exchange.

Needs of O2.
Reperfusion injury
THERAPEUTIC APPROACH

Intraluminal therapeutic approach.

Maintenance of Gut Wall.

Intravasal therapeutic measures.
INTRALUMINAL
THERAPEUTIC APPROACH

Peristaltic movement.
– Fibre application.


Bacterial adherence.
Bacterial elimination.
– SDD.

LPS Neutralization.
– Bile acids.
– Lactoferin.
– Lactulose.
MAINTENANCE OF GUT WALL

Splanchnic perfusion.
– Fluid support.
– TXA2 receptor blocker
– Angiotensin blocker.




Xanthin oxidase blockade.
NO – donors.
Metabolic support.
Growth factors support.
INTRAVASAL THERAPEUTIC
MEASURES

Bacterial killing.

LPS neutralization.
– LPS – antibodies.

BPI (Bactericidal permeability
increasing protein).

Inflammatory mediaters.
THERAPEUTIC APPROACH
4.2
LPS
LIVER
4.3
TNF
Systemic Circulation
Thoracic Duct
Kupffer Cells
Therapeutic Targets
Portal vein
Intraluminal
2
Bact/LPS
3
Gut Wall
NEW & FUTURE THERAPIES

Metabolic intestinal fuels.
– Glutamine.
– Shot-chain fatty acids (SCFA).


Intestinal growth factors.
Immunomodulation.
– Arginine.
– -3 fatty acids.

Antioxidants.
SELECTIVE
DECONTAMINATI
ON OF DIGESTIVE
TRACT