Metabolic responses to starvation

After 12 hrs Starvation

• Plasma Insulin Levels drop

• Glucagon Rises
• Hepatic glycogenolysis
• Muscle glycogenolysis
After 24 hrs

• Hepatic gluconeogenesis from proteins,

muscles

• 75 gram protein/day to 300 g of protein per

day may be lost
 Longer fasting
• Fat stores mobilized
• - glycerol and fatty acids
• - ketogenesis
• 2-3 wks brain adapts to use ketones instead of
glucose
• This reduces muscle breakdown
• ATP-dependent pathways are suppressed
Indications for nutritional intervention

Compromise in
• Physiology
• Immunity
• Wound healing
• Malnutrition
• Infections**
• Malignancy
 Indices
• Clinical History
• Body Composition Analysis
• Anthropometry
• Respiratory function
• Triceps thickness, Mid-arm circumference
• Biomarkers:
- Pre-albumin
TBP
Nitrogen balance
End-of-bed-ogram
 Nitrogen Balance
• measuring 24-hour losses

• 24-hour urine collection

• nitrogen loss is compared with nitrogen intake,

and nitrogen balance is thus obtained.

• Nitrogen balance = Intake - Loss (urine 90%,

stool 5%, others 5%)
 Measurements of Immunologic
Function
• Delayed cutaneous hypersensitivity (anergy)

• most commonly tested by delayed reaction to skin

antigens

• trauma or infection, anergy to injected cutaneous recall

antigens is associated with high mortality and morbidity

• Neutrophil function
 Glucose
• Glucose is the preferred carbohydrate source
in traditional TPN

• Infused glucose has nitrogen-sparing effect:

1. hepatic gluconeogenesis is suppressed.

2. glucose itself is an energy substrate, so fewer

amino acids need be oxidized for energy
• maximum suppression of gluconeogenesis is
achieved @infusion rates of 4 mg/kg/min
(∼400 g/day for a 70-kg man)

• @infusions rates higher than 9 mg/kg/min glucose

is degraded by nonoxidative pathways, leading to
net synthesis of lipid.
 Toxicity of Hyperglycemia and
Excessive Calorie Administration
• Excess carbohydrate is converted to fat in the liver
-de novo lipogenesis

• increase in Vco2 -impaired ventilatory function

• Immunosuppression

• increased frequency of nosocomial infections.

 Hyperglycaemia
Impairs
• chemotaxis
• Adherence
• Phagocytosis
• bactericidal function
• * immunosuppression*
 Hypocaloric feeding
• diabetic patient with difficult-to-control
blood sugar

• massively volume overloaded patient in renal

failure

• patient with poor oxygenation who is being

maintained on high ventilatory support
• reasonable protein goal - 1.5 g/kg/day

• total calories - 1000 kcal/day

• limit excessive volume administration

• obese patients- have large fat stores

 IMUNONUTRITION
• Glutamine –free amino acid in the extra and
intracellular compartments
• nitrogen transport
• acid base homeostasis
• fuel for rapidly dividing cells such as enterocytes,
lymphocytes and fibroblasts
• antioxidant defence mechanisms by influencing
glutathione synthesis
• severe stress or nutritional depletion the demand
< body's capacity to synthesise it.
 Glutamine-enriched parenteral
nutrition
• reduced length of hospital stay
• reduced costs
• improved nitrogen balance
• quicker lymphocyte recovery
• Glutamine has also been shown to maintain
intestinal permeability in postoperative
patients
• Vivonex
 Clinical examination
• Weight loss
• Anorexia
• Weakness
• inability to carry out normal functions
• disease process that interferes with intake, such as
esophageal carcinoma.
• burns, sepsis, head injury, and pancreatitis
• muscle wasting
• loose or otherwise abnormal skin
• edema of hypoproteinemia
• loss of body fat
• pallor
 Bioelectrical Impedance
Accumulation of lean body mass is the
principal objective of nutritional support

• Bioelectrical Impedance
• Exchange of Labeled Ions- Na , K
• Neutron Activation Analysis
• Computed Tomography
• Indirect Calorimetry (RQ)
• creatinine-height index
• triceps skinfold thickness
• Mid arm circumference
• ideal body weight (IBW) -before and after
 BMR
• Males
66+(13.7*Wt) + (5Ht)-6.8(Age)

Females
66.5+(9.6*Wt) + (1.7Ht)-(4.7*Age)
Carbohydrate:
• Gets used in 24hrs

Protein:
• Daily 60gm is used,
• 75 to 300 gm/day in post op

Fat
• Daily use 150g
• Higher in long starvation
 Cachexia of Cancer
• reduced food intake
• altered metabolic rate
• endocrine abnormalities
• anticancer treatments
• cytokines - TNF, IL-1, IL-6, and IFN-γ
• deranged central nervous system satiety
mechanisms
• Proteolysis-inducing factor (PIF).
• Marked muscle wasting in advanced cancer.

• increased rate of ATP-dependent proteolysis with

increased levels of mRNA for ubiquitin and subunits
of the proteolysis-inducing factor (PIF) activates the
ubiquitin-proteasome pathway in muscle

• treatment with eicosapentaenoic acid (EPA), blocks

formation of 15-hydroxyeicosatetraenoic acid by PIF
in muscle cells, inhibits weight loss even in those
with advanced disease
 Indications for Nutrition Support
• 1.    The patient's premorbid state (healthy or otherwise)   

• 2.    Poor nutritional status (current oral intake meeting <50%

of total energy needs)   

• 3.    Significant weight loss (initial body weight less than usual
body weight by 10% or more or a decrease in inpatient weight
by more than 10% of the admission weight   

• 4.    The duration of starvation (>7 days' inanition)   

• 5.    An anticipated duration of artificial nutrition
(particularly total parenteral nutrition [TPN]) of
longer than 7 days   

• 6.    The degree of the anticipated insult, surgical or

otherwise   

• 7.    A serum albumin value less than 3.0 g/dL

measured in the absence of an inflammatory state   

• 8.    A transferrin level of less than 200 mg/dL

  
• 9.    Anergy to injected antigens
 Additional variables
• Infections- upto 60%
• Thyrotoxicosis
• Metabolic disorders
• Short bowel
• Cancer patient
• Burns 110%
• Multi-organ failure
• Obstuctive pathology like Ca- Esophagus, Distal
Stomach
 BMR variations
Patient condition BMR
• No post op complications, • Normal
Fistula without infection

• Mild peritonitis, long bone • 25% above

fracture, mild-mod injury

• Severe injury, ICU infection, • 50% above normal

MOF

• 40- 100% Burns • 100% above normal

 Nutrition
• Calories- 25-35kcal/kg body wt

• Proteins- 1.5 g/kg

0.8 to 2 or 2.5g/kg body wt

• 1g nitrogen (6.25g protein) /150kcal/day

 Vitamins, Trace elements
• short-bowel syndrome

• extensive ileal resection

• pancreatic insufficiency
 Entero-hepatic Circulation

• Minerals-zinc, copper, manganese, selenium

• Vitamins -cobalamin, folate
• Fat-soluble vitamins A, D, E, and K
 DAILY DOSAGE
Vitamins:   Water soluble
• Thiamine 25 mg
• Riboflavin 25 mg
• Niacin 200 mg
• Pantothenic acid 50 mg
• Pyridoxine 50 mg
• Folic acid 2.5 mg
• Vitamin B12 5 mg
 Fat soluble  Vitamins
• A- 5000 μg

• D- 400 μg

• E 100 μg

• K 10 mg
 Trace Elements
• Zinc 10-20 mg
• Copper 0.5-2.0 mg
• Chromium 20 μg
• Selenium 70-150 μg
• Manganese 2-2.5 mg
• Iron 25 mg
 Supplementation

• Oral
• NG
• PEG
• Feeding Jejunostomy
• Parenteral nutrition
 Initiation of Nutrition Support
▪    Poor nutritional status (oral intake <50% of
energy needs)
▪    Catabolic disease
▪    Significant weight loss (>10%)   
▪    Anticipated duration of artificial nutrition
longer than 7 days     
▪    Nonfunctioning gastrointestinal tract   
▪    Serum albumin <3 g/dL *
 Enhanced recovery of patients after
surgery (‘‘ERAS’’)
• avoidance of long periods of pre-operative fasting;
• re-establishment of oral feeding as early as possible
after surgery;
• integration of nutrition into the overall management
of the patient;
• metabolic control, e.g. of blood glucose; electrolytes
• reduction of factors which exacerbate stress-related
catabolism or impair gastrointestinal function;
• early mobilisation
 EN advantages
• Prevents intestinal mucosal atrophy
• Supports gut associated immunological shield
• principal defense against an enteral osmotic
load
• Cheaper than TPN and has fewer
complications
 Routes for Administration of
Enteral Feeding

• Nasogastric tube
• Dobhoff tube
• feeding tubes with indwelling removable
metal stylet
• rigid plastic overtube
 Nasoenteric feeding tubes
• Duodenum/jejunum
• under fluoroscopic guidance/
• endoscopic manipulation and visualization
• ? risk for aspiration lessened
• Montecalvo and associates:
attained a significantly higher percentage of their daily caloric goal
** gastroparesis or with severe pancreatitis- useful
 Gastrostomy
• Stamm gastrostomy- a small laparotomy incision, LUQ

• PEG-
Necrosis of the gastric wall
Erythema, Induration
leak due to pull
granulation tissue with intermittent bleeding
continuous drainage.

• Percutaneous techniques-
Adhesions, colon perforation, open revision
 Jejunostomy
• open jejunostomy
• percutaneous -G-J tube
• percutaneous - fluoroscopic or CT guidance

continuous fashion feeding

watching for signs of intolerance
hypo-osmolar or at most iso-osmolar solutions
Risk of pneumatosis, necrosis, perforation, and death
 Gastric feeding
•Mortality
•Propped up position
•hypo-osmolar feeds first
•Then, increase osmolality & then volume
•? Gastric residual volume
•Avoid hyperosmolar feeding:
Pneumatosis bowel necrosis
Perforation mortality
 Formula Enteral Feeds
• Nepro, a high-density formula optimized for
renal failure, more fat & less protein, gluten-
and lactose-free
• Modular diets- protein, fat, and carbohydrate
components individually supplied
• Blenderized meal- for normal gut
• Impact With Fiber- Immune-enhancing tube
feeding for critical care; with fiber, high protein,
fish oil, RNA, arginine; gluten- and lactose-free
 Parenteral Feeding
• >900 mOsm/L
• CVL
• peripheral TPN (dextrose < 5%)
• Costly
• ? Benefit over enteral nutrition
• ? Complications
• Feed tailored??
 Indications
• Gastrointestinal cutaneous fistulas
• Renal failure (ATN)
• Short-bowel syndrome
• Acute burns
• Hepatic failure
• ?Crohn's disease, Anorexia nervosa ?
 Supportive Benefit
• Acute radiation enteritis

• Acute chemotherapy toxicity

• Prolonged ileus

• Weight loss preliminary to major surgery

• ? Prolonged ventilatory support

 TNA
Total nutrient admixture- 3 in 1
• 1. Limits the number of central venous catheter
violations and chance for contamination
• 2. Produces a hyperosmolar environment in the
TNA solution that protects against bacterial
growth
• 3. Allows continuous infusion, thereby ensuring
lipid administration at a safe rate (<0.11 g/kg/hr)
 common stock solutions
• 70% dextrose, 10% to 20% amino acids, and
20% lipid
• 1 L of solution in the absence of fat, the
maximal achievable concentrations are
7% amino acids (70 g/L) and 21% dextrose (210 g/L).
• Volume can be reduced with lipid
emulsification
 ions
• Calcium gluconate 9 mEq
• Magnesium 12 mEq
• Phosphate15 mmol
• Potassium chloride 80 mEq
• Insulin 100 units
 Preparing TPN
1st day TPN: 2 in 1
• 70g amino acids & 150 g dextrose in 1000 mL

2nd day:
• 70 g amino acids & 210 g dextrose

3rd day: 3 in 1
• Proteins , dextrose increased, fats added
PARAMETER DAY 1 DAY 2 DAY 3
Volume 1000 1000-1500 1500-2000
(mL/24 hr)

Calories 50% 75%, may add fat 100%

(% of goal)

Dextrose 100-150 150-200 200-350

(g/24 hr)

Amino acids 50%-100% 100% 100%, check BUN

(% of total)

Fat No Perhaps Often (3%-5%,

30-50 g/24 hr)

Insulin Give separately Add 50% to TPN Add 50% to TPN

 Mandatory Monitoring During
Intravenous Nutrition
Clinical:
Vitals
Daily fluid balance
body weight
Evidence of infection-
catheter infection
thrombophlebitis
• CVP
 Laboratory:
• Baseline & OD
- Electrolytes, BUN, creatinine, Ca, Mg,PO4
• Glucose Q6H

Weekly- liver function, coagulation

BASELINE:
• LFT, COAGULATION, ELECTROLYTES
 BMR

• Male BMR = 66 + (13.7×wt in kg) + (5×ht in

cm) - (6.8×age in yr)

• Female BMR = 65.5 + (9.6×wt in kg) + (1.7×ht

in cm) - (4.7×age in yr)
 25 to 35 kcal/kg/day
• patient is underweight –ABW

•  patient is obese (ABW is >120% of IBW)

add 25% of the difference between ABW and
IBW to the IBW as the feeding weight.   

•  If no reliable weight is available, use IBW alone.

IBW [Ht-152..]*0.91+50
 TPN Formulation
• STANDARD

• Non-STANDARD ( Prescription)
Hickmans Cath

Hickman, Broviac, Groshong

Port A Cath
 Complications- CVL
• Catheter Sepsis- Fungemia, S. epidermidis
• Catheter Thrombosis
• Pneumothorax
• vascular injuries (arterial or venous lacerations, delayed
arteriovenous fistulas)
• brachial plexus injury
• chronic pain
• thoracic duct injury
• air embolism
• Erosion of the catheter into the bronchus/ right atrium
Hepatic dysfunction
• Hyperbilirubinemia
• Hepatic steatosis, cholestasis
• cirrhosis and death in infants

Metabolic Bone Disease

• decreased bone mineral density
• increased urinary calcium or phosphate excretion
• decreased PTH levels
• vitamin D deficiency
 Pancreatitis

• severe hypertriglyceridemia

• glucose intolerance

• particularly if sepsis
Is preoperative metabolic preparation
of
the elective patient using
carbohydrate
treatment useful?
• Reduces insulin tolerance
• Reduces PONV
• But no diff b/w CHO drink and placebo
 Is postoperative interruption of oral
nutritional intake necessary after
surgery?
• Inadequate oral intake for more than 14 days
• Anticipated -unable to eat for 7–10 days
• intestinal obstructions or ileus
• severe shock
• intestinal ischemia
• <60% of caloric requirement via enteral
• Upper GI pathologies, fistulae
 When is perioperative nutritional
support
indicated?
• Cancer pt for major surgery

• immune modulating substrates (arginine, w-3

fatty acids and nucleotides)

• Preoperative EN- before admn to hospital

 Trends

• ω-3 fatty acids

• neutralizing antibodies to TNF
• glucocorticoid receptor antagonist RU-486
• glucagon-like peptide-2 (GLP-2)
• Insulin-like Growth Factors
• Growth Hormone
• ? testosterone