NUTRITIONAL SUPPORT IN NUTRITIONAL SUPPORT IN CRITICALLY ILLCRITICALLY ILL

Prof. Mehdi Hasan MumtazProf. 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 catabolism10-14 G N2 loss/day i.e. 294-420mmol UER/day.

Moderate to severe catabolism14-24 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

Protein urea

1GN2=6.25G of proteins

=1/6.25 x G of proteins

in urine

Rise of urea in blood

G x 28/60 x 60% B.W

Total N2 Loss = 1+2+3

ROUTES OF ADMINISTRATION

Enteral Parenteral RARE

Oral F Tube F Gastrostomy F Jejunostomy F

I/V Feeding Rectal Intrausternal Subcutaneous

Pain Allergy Absorption Infection

FLOW CHARTMalnutrition (Look)

(HALLMARKS)

YES

NO

YESNO

NOYES

ENTERAL PARENTERAL

(support indicated)GI Function

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.

REQUIREMENTSBASIC

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.

ENERGYSources

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

NeonatesG – 6 – PO4BARRIERF – 6 – PO4

GLUCOSE

G-6-PO4SORBITOL

FRUCTOSE

ACETALDEHYDE

ETHANOL

XYLITOL

d-XYLULOSE

6-PHOSPHO-GLUCONATE

RIBULOSE-5-PO4

NUCLEIC ACIDS

(PROTEIN SYNTHESIS)

G-6-PO4

F-1:6-DPO4

PYRUVATE

KREBS CYCLE

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 EFFECTSACUTE

Circulatory.– B.P Crisis. H.R.– Shock like.

Respiratory. respiration.– Cyanosis.– Dyspnoea.

Pain in chest – back. Nausea – vomiting. Flushing of skin. Pyrogenic reactions. Urticaria.

SIDE EFFECTSCHRONIC

Hyperlipaemia. Hepato-splenomegaly. Hepatic damage. Icterus. Anaemia. haemorrhage in G.I.T. Coagulation disorders with platelets. Pigmentation.

SOURCES OF NITROGEN

Blood Plasma

Poor Source Albumin Amino-acids

Catabolised to A.A first

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+

Reactions

Ideal A.A solution 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

VITAMINSTrace 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 /24 h

Zinc 2500-6000

Iron -

Copper 500-1500

Iodine -

Manganese 150-800

Florid -

Chromium 10-15

Molyhderium -

Selenium -

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 - daily. Related to liver - daily. Serum electrolytes - twice. Acid base status - twice. Special.

– 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

NUTRITIONAcute 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.

NUTRITIONHepatic Failure

Continuous use of lipids. Calories - bulk supply – hypertonic

glucose. Protein intake limited to 0.5G/kg/day. Eliminate protein in hepatic coma.

NUTRITIONRespiratory Failure

Excess glucose lipogenesis.

Excess glucose CO2 production.

50% non-protein calories – supplied by lipid.

STRESS ON

1. Specialised Nutrition Support In Critically Ill Patients.

2. Glutamine and Acute Illness.

PRESENT

&

FUTURE

SIGNIFICANCE OF GIT IN SIGNIFICANCE OF GIT IN CRITICALLY ILLCRITICALLY ILL

ANATOMY

&

HISTORY OF GUT

FUNCTIONS

Barrier

Transport

Endocrine

Barrier

Transport

Endocrine

BARRIER

Permeability & Permeation

Transcellular Paracellular

PORES

Large Small

(6.5nm) (0.4-0.7nm)

Surface area of:

- 2 million cm2.

- Single tennis court.

PERMEATION PATHWAYS

Paracellular Transcellular

(energy dependent) (small pores)

15% 85%

TIGHT JUNCTIONSZona Occludence)

ZO

Kisses + Pores

Permeability depends:

1. Hydrodynamic radius

2. Electrical charge.

3. Functional status of ZO

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. luminal microbial density.2. Damage to eipthelium.

– Irradiation.– Cytotoxic drugs.– Irritants.– Cytomegatovirus.– Mucosal disease.– Bowel manipulation.– Obstruction.– Free O2 radicals.

3. Diminished blood flow.– Haemorrhagic shock.– Burn.– Inflammtory agent.– Endotoxins.– M. occlusion.– Hypoxia.– Fever.

4. 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.

1. 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 L-

rhamnose 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 enterally7. %recovery lactulose to %recovery L-rhamnose ratio

calculated. Normal range 0-0.08.

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).

ARGININE1. Production and secretion.

– Pitintary GH.– Protaction.– IGF-1.– Glucagon.– Somatostatin.– Pancreatic polypeptide.– Nor-epinephrin.

2. Pre-cursor of growth factors.– Putrescine.– Spermine.– Spermidine.

ARGININE

3. Produce NO.

4. Resistance.

5. T-cell immunity.

6. Wound healing.

7. Cancer growth.

8. Protein content.

9. Lymphocyte nitrogen & allogenic response.

10. 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

Pancreatic & biliary secretions

Autonomic CNS

enterohormones

Dilatation & mesenteric blood flow

Intestinal cell proliferation & differentiation

Endocrine effects

paracrine effects

METABOLIC STRESSStarvation+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 ILLNESSHypermetabolism

+

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 HypoxiaVillous counter current

exchangingO2 Supply.Perfusion.

Mitochondrial oxidation

Anaerobic Metabolism

Less ATP

Cytoskeleton Integrity

Permeability

RO Metabolits

G-3P

ATP+

MitochondrialPhosphorylation

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

TNFLPS

LIVER

Kupffer Cells

Systemic Circulation

4.34.2

Thoracic Duct

Portal vein

Intraluminal Bact/LPS2

Gut Wall

3

Therapeutic Targets

NEW & FUTURE THERAPIES

Metabolic intestinal fuels.– Glutamine.– Shot-chain fatty acids (SCFA).

Intestinal growth factors. Immunomodulation.

– Arginine. -3 fatty acids.

Antioxidants.

SELECTIVE DECONTAMINATION OF DIGESTIVE

TRACT