Pranithi Hongsprabhas MD Division of Clinical Nutrition, Department of Medicine, Faculty of Medicine KKU

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Pranithi Hongsprabhas MDDivision of Clinical
Nutrition, Department of Medicine, Faculty of
MedicineKKU

• Update in Clinical Nutrition

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• Surgery

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Surgery

• Focus of perioperative management is Enhanced
  Recovery of patients After Surgery (ERAS)
• Surgery does influence response of nutrition
  support
• Peri-operative routines also have major impact
  on nutritional tolerance

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Surgery

• Surgery injury ? altered metabolism
• Stress hormones
• Inflammatory mediators cytokines
• Catabolism of
• Glycogen ? glucose
• Fat ? fatty acid, glycerol
• protein ? amino acid
• Substrates for
• Immune response
• Physical activity/rehab need anabolism
• Healing

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Surgery

• Measures to minimize stress can minimize
  catabolism and enhance anabolism
• Enhanced Recovery of patients After Surgery
  (ERAS)
• Combine measurers to minimize stress and
  facilitate return of function

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ERAS

• Preoperative preparation
• Medication
• Fluid balance
• Anesthesia
• Postoperative analgesia
• Pre-post operative nutrition
• Mobilization

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Length of hospital stay

• Type of operation
• Perioperative blood loss
• Degree of postop insulin resistance and
  hyperglycemia
• Size of operation
• Any complication
• Last 2-3 wk
• Post op hyperglycemia treatment reduce morbidity
  and mortality

Van Den Berghe Et Al, NEJM 2001
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Intensive Insulin TreatmentVan Den Berghe Et
Al, NEJM 2001
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Perioperative routines

• Preoperative fasting
• Necessary?
• Is preop metabolic preparation of elective pt
  using CHO Rx useful?
• Postoperative interruption of oral intake
• Unnecessary (A) oral intake should adapt to
  individual tolerance and type of surgery
• Oral intake can be initiated within hr after
  colon resection (A)

ESPEN Guidelines on ENSurgery including organ
transplantation. Clin Nutr 2006
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• Reduction of insulin postoperative resistance
• Preoperative preparation CHO solution
• Pain control
• Factors affects GI tolerance
• Opiate
• Fluid management
• Minimal invasive and gentle surgical technique

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Severe undernutrition has long been known to be
detrimental outcome

• Evidence
• Inadequate oral intake forgt14 d is associated
  with higher mortality1
• Prevention and treatment of undernutrition
• (when prolonged fasting and/or severe catabolism
  are expected)
• Morbidity, LOS and mortality are principle outcome

Sandstrom R et al. Ann Surg 199316185
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When is Preop EN indicated?

• Severe nutriitonal risk benefit from NS for 10-14
  d prior major surgery, even if surgery has to be
  delayed.
• Wt loss 10-15 within 6 mo
• BMI lt 18.5
• SGA class C
• Alb lt3
• Whenerver possible EN preferred (without delay)
• Preop GI cancer immunonutrition

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Combined ENPN

• EN is indicated when
• Pt will be unable to eat gt7 d postop
• Pt cannot maintain oral intake above 60 for gt10
  d
• EN is contraindicated in
• Intestinal obstruction or ileus
• Severe shock
• Intestinal ischemia
• Indicate for nutrition support and in whom energy
  needs cannot be met (lt60) by EN

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Application Preop

• Encourage ONS preop in pt who do not meet
  requirement from normal food (C)
• Pt undergoing surgery, no specific risk of
  aspiration, may drink clear fluid until 2 hr
  before anesthesia. Solid are allowed 6 hr (A)
• Preop CHO load (the night before and 2 hr before
  surgery) is recommended in pt undergoing major
  surgery (B)

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Application Postop

• Initiate normal food intake or EN feeding early
  after GI surgery
• Oral intake, including clear liquids, can be
  initiated within hrs after surgery to most pt
  undergoing colon resection
• Oral intake should, however be adapted to
  individual tolerance and type of surgery

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Application Postop

• TF in whom EON cannot be initiated
• Head/neck, GI cancer (A)
• Severe trauma (A)
• Obvious undernutrition at the time of surgery
• Oral intake will be inadequate (lt60) for gt10 d
  (A)
• Initiate TF within 24 hr after sugery (A)
• Start with a low rate (10-20ml/hr)
• May take 5-7 d to reach target

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Type of tube feeding

• Needle catheter jejunostomy or naso-jej for all
  candidate for TF undergoin major abd surgery
• When anastomosis is the proximal GI performed,
  deliver EN vial tube placed distally to
  anastomosis
• Consider PEG if long term TF

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Type of formula

• Most patients standard
• Immunomodulating nutrition perioperatively
  independent of nutritional risk for
• Major head and neck cancer surgery
• Major abdominal cancer surgery
• Severe trauma
• Whenever possible
• Give 5-7 d preop
• Give 5-7 d postop

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Conclusion

• Avoidance of long period or pre-op fasting
• Reestablishment of oral feeding as early as
  possible after surgery
• Integration of nutrition into the overall Rx of
  pt
• Metabolic control
• Reduction of factors exacerbate stress related
  catabolism or impair GI function
• Early mobilization

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• Case discussion in nutrition

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Critical illness/Acute pancreatitis

• 45 yr old, previously healthy man was admitted
  with severe abdominal pain. No medical history,
  alcoholic.
• PR 120, Bp 100/60 urine 25 ml/hr.
• generalized guarding, ileus.
• Amylase gt2000 SIu Na 135, K 3, Hb 11 g/dl, WBC
  25000, Bili 4.5 ALT 450, Alb 36g/l, hypoxic.
• CXR Lt pleural effusion
• BW 70 kg. Ht 1.8m

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Acute pancreatitis

• Diffuse inflammation pancreas with variable
  involvement of regional tissues and/or remote
  organ system
• Severity
• 80 mild
• 20 severe
• Auto-digestion of glands
• premature activation of lytic enz or by
  disruption of balance between activated protease
  and protease inhibitor
• Etiology
• alcohol, stone, idiopathic, etc

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Nutritional aspects

• Nutritional deterioration
• Reduce intake
• Stress
• Maldigestion/absorption
• Fistula
• Concept of pancreatic rest
• Decrease pancreatic exocrine secretion/stimulation
  
• Reduce secretion may sufficient
• Rx strategies to rest pancreas failed to show
  impact on clinical outcome in severe cases

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Stimulation of pancreatic secretion

• Multiple factors
• Neural (vagal)
• Chemical luminal aa, fat, gastric acid
• Hormones gastrin, secretin, VIP, CCK
• Mechanical distension of gastric wall
• Effect of IV nutrients inconclusive
• No effect of IV nutrients (6/7)
• Effects of EN on pancreatic inflammation
• Early oral diet worsen exacerbation (21), true
  exacerbation of disease (4.3)

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Critical illness/Acute pancreatitis

• What would be your strategy for fluid Rx at this
  stage?
• Which aspects of the foreseen clinical course
  are potentially relevant for metabolism and
  nutrition?
• What is his nutritional status?
• is he nutritional depleted, or at risk?
• Would you start nutrition support, an if yes, why
  and how?

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Fluid Rx considerationCritical illness/Acute
pancreatitis

• maintenance ECF resuscitation
• consider
• sequestration --gt hypovolemia
• prerenal vs acute renal failure
• impending lung injury / ARDS

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Case StudyCritical illness/Acute pancreatitis

• Foreseen clinical course potentially relevant for
  nutrition and metabolism
• Hyper metabolic/catabolic
• ileus
• electrolyte imbalance hyponatremia,
  hypo/hyperkalemia
• hyperglycemia
• hypertriglyceridemia decreased LPL activity

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Case StudyCritical illness/Acute pancreatitis

• Patients nutritional status
• Not depleted but at risk

• Nutritional screening
• BMI normal 0
• no weight loss 0
• nearly no food intake 1
• hypermetabolic/catabolic2
• Score3
• previously normal status
• Close F/U if not improve perform nutrition
  assessment

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Hierarchy of Vital Organ System

• Immediately relevant for survival
• circulation
• CNS
• respiratory system
• Relevant for survival with delay
• splanchnic organ
• metabolism

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Case StudyCritical illness/Acute pancreatitis

• Rational for early ANS
• Pancreatitis
• hypermetabolic/catabolic
• prolonged inadequate food intake
• risk of nutritional deterioration
• Malnutrition
• adverse effect on host defense, immune competence
• worsen outcome MR 2.5 vs 21.4 in pt unable to
  achieve N balance Sitzmann JV, et al. Surg
  Gynecol Obstet 1989

• Rational against early ANS
• No PRCT exists to show that early ANS reduces the
  duration or lessens the severity of disease when
  compare to no NS
• Early NS(TPN) is associated with complications.
  Sax et al. Am J Surg 1987.
• Early return of oral diet or displacement of jej
  feeding back to stomach associates with
  exacerbation of pancreatitis. McClaves SA, et al.
  JPEN 1997

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Case StudyCritical illness/Acute pancreatitis

• progressive deterioration of clinical
• CT performed D 3 of admission

• Percutaneous aspiration of necrosis for C/S, G/S
• Antibiotic started

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Critical illness/Acute pancreatitis D5 ARF,
ARDS, C/S reveals E coli.

• Would you start SNS, and if yes, why and how?
• What are the risks of PN vs EN at this stage?

• Yes, because complication arises
• hypermetabolic/catabolic
• Via naso-jejunostomy elemental or polymeric but
  small amount
• combined PN

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Case StudyCritical illness/Acute pancreatitis

• D9
• surgical removal of infected necrosis was done
  due to persistent ileus and progressive sepsis.
• Jejunostomy and ileostomy
• Regular HD
• worsening ARDS/ on PCV/PEEP

• Would you start SNS already?
• What is your estimated the patients TEE?
• How much N/d is the patient likely to lose, if
  not fed?

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Nitrogen and energy balance response to nutrition
N intake ---gt
Energy intake --gt
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Argument for parenteral nutrition

• Need to reduce stimulation and secretion of
  proteolytic enzymes
• PN least likelihood of pancreatic stimulation
• easily access
• Nutritional goal achieved quickly and easily

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Argument for enteral nutrition

• Without EN associates with
• Gut atrophy may be source for systemic endotoxin
  and sepsis Winsor AC. Gut 1998
• bacterial translocation to pancreatic tissue.
  Russel JC. Am J Surg 1983.

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Argument for enteral nutrition

• EN
• pancreatic stimulation?
• Pancreatic exocrine function reduces
• CCK stimulated secretion be abolished
• recovery of secretory function takes time
• feeding low in GI(distal to ligament of Treitz)
  does not stimulate pancreatic secretion Grant JP.
  JPEN 198.7, Keith RG.Surg Gynecol Obstet 1980.

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Comparison of the safety of early enteral vs
parenteral nutrition in mild acute pancreatitis.
Evidence based data

• RESULTS
• no differences on admission in mean age, Ranson
  criteria, MOF, or APACHE III score
• no differences between groups in serial pain
  scores, days to normalization of amylase, days to
  diet by mouth, serum albumin levels, or percent
  nosocomial infection. However, the mean cost of
  TPN/pt was x 4 than TEN (p lt .001).
• Mean serial Ranson criteria, APACHE III, and MOF
  decreased in the TEN , whereas increase in the
  TPN group.
• Difference in the 3rd Ranson criteria (mean 6.3
  days) for the TEN and TPN groups (0.5 vs 2.8,
  respectively) (p .002).
• Stress-induced hyperglycemia worse in the TPN
  group, (p lt .02), whereas no significant change
  in the TEN group.
• CONCLUSIONS TEN is as safe and effective, may
  promote more rapid resolution of the toxicity and
  stress response.
• TEN via jejunal feeding should be used
  preferentially in this disease setting.

McClave, S. A. et al. JPEN J Parenter Enteral
Nutr. 1997.
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Compare with PN, EN attenuates the acute phase
response and improves disease severity in acute
pancreatitis
Windsor ACJ, et al. BMJ 1998 42(3) 431-5
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Enteral nutrition is superior to parenteral
nutrition in severe acute pancreatitis Results
of a randomized prospective trial.

• 38 pts with acute severe pancreatitis were
  randomized into 2 grs.
• EN gr(n 18) received EN through a NJ with a
  semi- elemental diet
• PN gr(n 20) received PN through a central
  venous catheter.
• Safety, N balance,cost
• RESULTS
• EN was well tolerated without adverse effects on
  the course of the disease.
• EN gr experienced fewer total complications (P lt
  0.05) and lower risk of developing septic
  complications (P lt 0.01) than those receiving
  parenteral nutrition.
• The cost of nutritional support was3 times higher
  in PN gr.
• CONCLUSION This study suggests that early enteral
  nutrition should be used preferentially in
  patients with severe acute pancreatitis.

Kalfarentzos F, et al. Br J Surg 1997 84 1665-9
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Randomized controlled trial of the effect of
early enteral nutrition on markers of the
inflammatory response in predicted severe acute
pancreatitis
Powell JJ, et al. Br J Surg 2000 87 1375-81
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Clinical trials of EN in severe pancreatitis
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Enteral vs. parenteral nutrition for acute
pancreatitis
Al Omran M, Groof A, Wilke D. Cochrane Review.
In The Cochrane Library, Issue 3, 2002
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Enteral vs. parenteral nutrition for acute
pancreatitis
Al Omran M, Groof A, Wilke D. Cochrane Review.
In The Cochrane Library, Issue 3, 2002
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Safety of Early enteral nutrition (EEN)

• No significant difference in medical outcome PN
  vs EN
• Days to normalize amylase, oral diet, LOS, ICU
  stay and mortality
• Site of feeding
• lower in GI invoke fewer stimulation of
  pancreatic secretion (stimulate inhibitory
  factors PIP, PP, bile salt)
• Decrease SIR markers
• Nutrients and pancreatic stimulation
• Fat gt fat free
• LCT gt MCT
• intact proteingt peptides
• Tolerance variable, depends on severity,
  necrosis
• Gut integrity largest immune organ
• Mucosa, blood flow, GALT can be maintained by EN
• Local immune response

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Acute pancreatitisESPEN 2002

• Nutrient requirements
• energy B2535 kcal/kg BW/dayprotein 1.21.5 g/kg
  BW/day
• CHO 36 g/kg BW/day corresponding to blood
  glucose concentration
• lipids up to 2 g/kg BW/day corresponding to blood
  TG
• SNS start with TF by a jejunal feeding (when
  caloric goal cannot be reached, give additional
  PN)
• nutrition with a small content of an elemental
  (1030 ml/h)
• continuously perfused to the jejunum.
• When EN is not possible, give PN

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ESPEN Guideline 2006 in acute pancreatitis
Indication

• Mild acute
• nutrition support is unnecessary if resume normal
  diet after 5-7 d (B)
• EN within 5-7 d, no ve impact (A)
• TF if oral diet not possible gt5 d (C)
• Severe necrotizing
• EN is indicated if possible (A)
• EN should be supplemented by PN if needed (C)
• With complicated disease (fistula, pseudocyst) TF
  can be performed successfully

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ESPEN Guideline 2006 application

• TF is possible in major of diseases, but may need
  PN supplement (A)
• Oral feeding can be progressively progress once
  gastric outlet obstruction, complication under
  control (C)
• Severe case continuous EN in all who tolerate it
  (C)

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ESPEN Guideline 2006 for route

• Jejunostomy feeding is preferred if gastric
  feeding cannot be tolerated (C)

ESPEN Guideline 2006 for formula

• Peptide base formula can be used safely (A)
• Standard formula can be tried if tolerated (C)

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Critical illness/Acute pancreatitis

• D11-20 patient has improved lung function and gas
  exchange still on heavy sedation
• EN has been started but retention remains a
  problem
• What are the potential metabolic effect of
  sedative agents, and are there different between
  drug in this aspect?
• Would you use prokinetic agent? If so, are there
  any risks associated with prokinetic?

• Sedation decrease REE
• propofol contain lipid and give high calorie
• probably use prokinetic with caution
• evidence of bowel necrosis with using prokinetic

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Critical illness/Acute pancreatitis

• D25 His clinical improved but lost substantially
  his muscle mass and the FVC was markedly reduced
• Would either of these findings have any
  consequences for the nutrition strategies?
• Which factors can contribute to the deterioration
  of muscle function?
• What is the clinical relevance of deteriorated
  muscle function in this setting

• No
• protein catabolic, CIP/CIM
• difficult weaning--gt VAP, repeated SIRS

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Case StudyCritical illness/Acute pancreatitis

• D33 Pt remain on MV with unsuccessful weaning
  attempts. Infection was under controlled
• which metabolic factors could contribute to
  difficult weaning/
• Would you modify your feeding strategy during
  weaning?

• Overfeeding --gtVCO2
• hypermetabolic--gtVO2
• look for overfeeding
• explore for muscle wasting patient
  (clinically)--gt put to respirator, respiratory
  rehabilitation

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Nutrition in Ventilatory Failure

• Ventilator dependency
• mismatch between ventilatory demand and capacity
  to perform work of breathing
• overfeeding worsening mismatch
• increased VCO2
• underfeeding may worsen mismatch
• loss of muscle

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Respiratory Quotient (RQ)

• RQ
• Glucose oxidation 6/6 1.0
• 1 glucose 6 O2 6 CO2 6 H20
• Fat oxidation 16/23 0.7
• 1 palmitate 23 O2 16 CO2 16 H2O
• Protein oxidation 4.1/5.1 0.8
• 1 amino acid 5.1 O2 4.1 O2 2.8 H2O
• Lipogenesis gt 1.0 8.0

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Metabolic Response to Overfeeding

• Hyperglycemia
• Hypertriglyceridemia
• Hypercapnia
• Fatty liver
• Hypophosphatemia, hypomagnesemia, hypokalemia

Barton RG. Nutr Clin Pract 19949127-139
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Advance Pulmonary Disease ASPEN 2002
At 1.3 REE
Effect of Feeding
Fixed CHO fat
Talpers S.Chest 1992102551
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• Adult Renal failure

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Acute renal failure

• Abrupt cessation or decline in renal function
• Etiology
• Prerenal
• Postrenal
• Intrarenal
• Clinical course
• Initiation
• Maintenance
• Recovery

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ARF

• General
• Fluid
• Overload
• Electrolytes
• K, P retention

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ARF dialysis support

• PD not commonly used
• IHD/ CRRT
• HD 3/wk, 3-4 hr/session
• CRRT causes less hemodynamic changes, grater
  clearance, tight control metabolic derangement
• Hybrid dialysis
• Slow, low efficiency dialysis (SLED) 6-12
  hr/session, 6-7 d/wk

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ARF nutrition aspects

• Metabolism
• Effects of underlying disease/co morbidities
• Effects of treatment
• Effects of other organ dysfunction
• GI function motility, absorption, bleeding
• Energy according to underlying causes
• CHO
• High insulin resistance gluconeogenesis
• hyperglycemia
• Fat
• Impairment of lipolysis

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ARF nutrition aspects

• Protein
• Increased protein catabolism breakdown of muscle
  protein and abnormal use of aa by muscle
• Accelerated protein breakdown
• Gluconeogenesis
• Insulin resistance
• Acidosis
• Cytokines
• Counter regulatory hormone
• Abnormal aa metabolism by ARF
• Glutamine, arginine,histidine

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Acute renal failureNutritional requirement in ARF
Energy 20-30 kcal/kg/d
CHO 3-5 (max7) g/kg/d
Fat 0.8-1.2 g/kg/d
Protein (EAA/NEAA)
Conservative 0.6-0.8 g/kg/d
Extracorporeal Rx 1-1.5 g/kg/d
CCRT, in hypercatabolism Up to maximum 1.7g/kg/d
ESPEN Guideline on EN Adult Renal Failure. Clin
Nutr 2006
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• Liver Diseases

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Liver diseases

• Prevalence
• uncommon in non cirrhotic/compensated cirrhosis
• common in decompensated cirrhosis, severity
  correlates with liver dysfunction
• Characteristic of PEM are influenced by etiology

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Pattern of Malnutrition in Chronic Liver Disease Pattern of Malnutrition in Chronic Liver Disease Pattern of Malnutrition in Chronic Liver Disease Pattern of Malnutrition in Chronic Liver Disease
Muscle wasting Fat loss Reduced synthetic function
Alcohol Severe Mild Moderate
Viral Moderate Moderate Mild
Promary biliary cirrhosis Severe Severe Mild
Primary sclerosing cholangitis Moderate Mild Mild
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Protein Energy Malnutrition in Liver Diseases
Reduced intake anorexia satiety nausea and vomiting unpalatable (protein, salt restriction
Malabsorption bile salt def pancreatic def enteropathy
Altered metabolism alcoholic toxicity to E and P metabolism protein break down and aa oxidation accelerate fat oxidation gluconeogenesis
Fasting diagnostic test GIB HE
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Metabolic alteration in cirrhosis

• Accelerated starvation fat oxidation
• Protein imbalance
• Skeletal muscle breakdown
• HE 3rd most common of death (20)
• Subclinical HE 70, not require specific Rx
• HE (NH3, mercaptans, FA, - aminobutyric, altered
  aa, endogenous BZD)
• Overt HE
• 95 has precipitating factors
• 5 pp by protein
• 95 tolerate diets of proteins (upto 1.5g/kg/d)

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Metabolic alteration in ALD

• Alcohol
• has deleterious effects no muscle protein
• inhibit meal stimulated hepatic protein synthesis
• increase intestinal permeability
• provide empty calorie
• 7kcal/g
• Replace nutrient energy
• Induce cirrhosis

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Objectives of nutritional Rx

• Prevent of slow catabolism to prevent or correct
  PCM
• Attain optimal glucose control
• Sustain energy balance
• Correct or prevent vitamin/trace element
  deficiencey
• Improve hepatic function/regeneration
• Reversla of existing HE, and prevention
• Reduction of ascites and edema
• Preparation for transplant

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Background

• SNS is less relevant if acute liver failure than
  chronic liver disease
• GI functions adequately in most allowing
  correction of nutritional deficits
• Fat oxidation predominant profile of cirrhosis
  should avoid fasting
• Diet composition depends on type of liver
  diseases
• Mildly decompensate high cal-prot, low Na
• TF inmprove liver function and HE

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ESPEN Guideline for SNS alcoholic hepatitis

• Recommend
• Energy 35-40 kcal/kg/d
• Protein 1.2-1.5 g/kg/d
• ONS recommended
• Type of formula
• Whole protein formula
• Consider more concentrated high energy formulae
  in pt with ascites
• BCAA formula in HE arising during EN

ESPEN Guidelines on EN Liver disease. Clin Nutr
2006
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ESPEN Guideline for SNS Cirrhosis

• Recommend
• Energy 35-40 kcal/kg/d
• Protein 1.2-1.5 g/kg/d
• Use supplement when cannot meet requirement (ONS
  or TF)
• Type of formula
• Whole protein formula
• Consider more concentrated high energy formulae
  in pt with ascites
• BCAA formula in HE arising during EN

ESPEN Guidelines on EN Liver disease. Clin Nutr
2006
74
Outcome

• Improves nutritional status
• Improve liver function
• Prolonged survival

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Nutrition recommendation
Cachexia 120 of estimated EE, increased cal if malabsorption or malnutrition amall, frequent meals
HE Maximize medical Rx, identify and Rx PP factor Restrict protein only if protein sensitive (0.5-0.7 g/kg/d) and increase to tolerance up to 1.5g/kg/d Consider nutritional supplement BCAA if intolerance to std protein
Ascites/Edema Na restriction
Hyponatremia Restrict water 1-1.5l/d
Hyperglycemia CHO control meal/ insulin
Hypoglycemia Frequent meals or snack
Steatorrhea Restrict fat, try MCT, supplement fat soluble vitamin
Osteopenia Maintain appropriate wt, balance diet Provide enough protein to maintain muscle mass Ca 1.5g/d, enough vitamin D Avoid alcohol
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• Nutrition in Cancer

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Weight Loss in Cancer Patients

• 80 of cancer pt lose wt
• Wt loss is prognostic significant

Kondrup AJCN 2002, De Wys et al. Am J Med 1980,
Andreyev et al. Eur J Cancer 1998
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Cancer Cachexia Myth

• Anorexia-cachexia syndrome is due to the host
  lack of appetite and or starvation
• Anorexia-cachexia happens because of tumor
  consumes the host nutrients

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Progression of Cancer-induced Weight Loss
Normal
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Cancer Cachexia

• Syndrome of combined physiologic, metabolic and
  psychological factors
• Manifestations
• anorexia
• progressive involuntary wt loss, wasting, tissue
  depletion
• Fatigue, poor performance
• Anemia
• More advance disease higher risk of wt loss

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Cancer Cachexia Anorexia Syndrome (CACS)
Abdominal pain
Malabsorption
Depression
Cachexia
Taste alteration
Constipation
Radio/chemotherapy, surgery side effects
Intestinal obstruction
Derangement of Metabolism

• Increased
• Lipolysis/lipid metabolism
• Proteolysis
• REE

• Decreased
• Lipogenesis
• LPL activity
• Protein synthesis

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Does nutritional status influence the clinical
course and the prognosis?

• Reduce QOL
• Lower activity level
• Increase treatment related adverse reactions
• Reduce tumor response to treatment
• Reduce survival

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Does cancer influence energy expenditure?

• Cancer itself does not have consistent effect on
  REE
• Increased ¼ had 10 higher than predicted
• Unchanged
• Decreased ¼ had 10 lower than predicted

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Carbohydrate Metabolism

• 1925 Cori Cori demonstrate decreased glucose
  level
• High anaerobic glycolysis
• Glucose to lactate
• Increased lactate level
• Lactate
• Oxidized 15
• Regenerate to glucose 85

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CHO Metabolism

• Gluconeogenesis increased
• Lactate, glycerol, alanine
• Cannot be suppressed by glucose supplement
• Decreased glucose tolerance insulin resistance

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Lipid Metabolism

• Depletion of fat store
• The proportion of wt loss fat loss
• Associated with hypertriglyceridemia
• Increased lipolysis, FFA and glycerol turnover
• Normal or increased lipid oxidation
• Decreased lipid clearance
• Decreased lipoprotein lipase (LPL)

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Protein Metabolism

• Increased protein metabolism
• Whole body protein turnover unchanged
• Muscle tissue largest pool
• Muscle protein loss, muscle wasting
• Decreased protein synthesis

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Energy requirement

• If REE cannot be measured, use rule of thumb
• Ambulant pt 30-35 kcal/kg/d
• Bedridden pt 20-25 kcal/kg/d

• Oncological Rx may modulate EE

92
Do cancer patients require a distinct nutrient
composition?

• Standard formula are recommended for EN of cancer
  pt
• Protein 1 g/kg/d (minimum)
• 1.2-2 g/kg/d
• Supplement with electrolyte, vitamins and trace
  element acording to RDA

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What are specific nutritional goals in cancer
patients?

• Prevent and treating undernutrition
• Enhancing anti-tumor treatment effects
• Reducing adverse effects of anti-tumor Rx
• Improve QOL

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When should EN be started?

• If undernutrition already exists
• If it is anticipated that Pt will be unable to
  eat for gt 7 d
• If an inadequate food intake (lt60) to eat for gt
  10 d

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Can EN maintain or improve nutritional status in
cancer patients?

• Yes In wt lost patients from insufficient
  intake
• Gain more wt, lost less wt1
• improve or maintain nutritional status2
• maintain QOL

1. Systematic review of ONS, counceling Baldwin
et al, 2004 2. Cancer cachexia and GI cancer
Bozzetti F1989 and Lindh A 1986. 3. GI and H
neck cancer. Isenring EA, 2004
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Can EN maintain or improve nutritional status in
cancer patients?

• In the presence of inflammation
• Extremely difficult to achieve anabolism
• Without effective antitumor Rx, it is impossible
  to reverse this process
• At least to maintain wt or minimize wt loss
• Additional intervention pharmacological effort
  recommended to modulate inflammatory response

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Can metabolic modulators increase nutritional
intake

• Steroids (short term)
• Improve appetite
• Nausea
• Pain
• Progesterone
• Improve appetite
• Wt gain
• QOL
• ?-3 fatty acid less active pro-inflammatory
  midiators
• Improve appetite and body weight

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Does supplementation with ?-3 fatty acid have
beneficial effect in cancer patients?

• RCT contradictory/controversial
• Evidence level C
• RCT
• improve survival/Non significant effect on wt
• Did not improve wt or appetite
• Non RCT improve survival, side effect of CTX
• Recent RCT high dose EPA wt stabilization, wt
  gain
• Unlikely to prolong survival in advance cancer
• The result of further trials are awaited

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Special situation

• Perioperative EN
• Radiotherapy
• Chemotherapy
• Transplantation
• Advance stage/ incurable

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Perioperative

• Severe nutritional risk benefit from nutritional
  support 10-14 d prior to major surgery even if
  surgery has to be delayed (A)
• All cancer pt undergoing major abdominal surgery,
  preop EN preferably with immune modulating
  substreates (Arg, n-3 fatty acid, and
  nucleotides) 5-7 d independent of nutritional
  status (A)

101
Is there indication for EN during radiotherapy
(XRT)or combined radiotherapy(cXRT)?

• Yes, use intensive counceling and ONS to increase
  intake (A)
• to prevent Rx associated wt loss
• To prevent interuption of XRT
• in GI, head and neck area
• If obstructive HN or esophageal CA interferes
  with swallowing tube feeding is preferred
• TF is preferred if local mucositis is expected
  (c)
• Routine EN is not indicated during XRT of other
  body regions (c)

102
Is there indication for EN during chemotherapy?

• No
• Routine EN during CTX has no effect on tumor
  response nor CTX associated unwanted effects (b)

103
Is there an indication for EN in advanced stages
of incurable cancer patients?

• EN should be provided in order to minimize wt
  loss, as long as pt consents and the dying phase
  has not started (c)
• When EOL is very close, most pt require only
  minimal of food and water to reduce thirst and
  hunger (b)

104
Risk of EN

• Does EN feed the tumor?
• No reliable data
• Theoretical considerations should
• No influence of the decision to feed a cancer
  patient

105
Conclusion

• Complete improvement of nutritional state is not
  attained in short time
• Cancer Rx should not be postponed until
  nutritional rehabilitation achieved
• Nutritional Rx should be incorporated in to the
  overall Rx as early as possible
• Effort to improve nutritional and metabolic
  status may decrease morbidity and mortality in
  pts who need surgery, XRx, CRx

106
An CAM Rx should be discouraged if

• Delays conventional Rx
• No scientific prove
• Provided by unlicensed practitioner
• Require injection of substances not approved by
  FDA

107
Chronic renal failure Scope

• Protein energy malnutrition in CKD
• Effect of nutritional Rx on progression of CKD
• Nutritional therapy predialysis
• avoid uremic toxicity
• avoid malnutrition

108
Prevalence of PEM

• PEM common in advance stage of CKD
• 40 Ikizler TA. J Am Soc Nephrol 199561386
• 10-70 of MHD. Bergstrom J. Kid Int 1993 43S39.
• 18-51 CAPD Bergstrom J. Kid Int 1993 43S39 or
  40 and 8 severe. Young GA. AJKD 1991 17
  462-471.
• Become clinically evident when GFR lt5-10 ml/min
• Characteristics of PEM in CKD

109
Relationship Between Malnutrition and Morbidity
and Mortality

• PEM in CKD is related to poor clinical outcome
• body protein reserve lt 80 had 1 year mortality
  rate gt normal 4.1 x
• Low albumin strongest predictor of death risk
• albumin 3.51- 4.0 2.21
• albumin lt 2.5 7.45
• Prealbumin lt300 mg/l associated with higher
  mortality

110
Malnutrition Syndrome in ESRD

• ESRD pts develop a state similar to chronic
  malnutrition
• Not appear to be corrected simply by adequate
  dialysis.
• Malnutrition and uremia have synergistic effect
  on lymphocyte function and cytokine response

111
Effect of PEM on Renal Function

• Impaired ability to eliminate acid and solute
  load
• Reduced renal plasma flow
• Reduced GFR and urine concentrating ability

Klahr S. Effect of malnutrition and of changes in
protein intake on renal function.in Nutritional
management of renal disease. 1997229.
112
Mechanism Responsible With PEM in Chronic Kidney
Disease Multifactorial

• Poor intake
• abnormal lipid and CHO metabolism
• amino acid imbalance
• abnormal hormonal response
• loss of nutrients in dialysis (4-10g aa/HD, 5-15g
  prot/d in PD)
• uremic toxicity and metabolism

113
Metabolic Acidosis

• Increased cortisol, BCKA dehydrogenase activity
• proteolysis
• protein breakdown, aa oxidation
• negative N balance
• decreased albumin synthesis
• impaired insulin activity and glu utilization
• correction of MA improves N and nutritional status

114
Hyperparathyroidism

• Impaired protein metabolism
• Insulin resistance
• impaired protein metabolism

115
Potential Causes of Inflammation in PD

• General causes
• Reduced renal clearance of cytokines
• Chronic heart failure
• Atherosclerosis per se
• Various inflammatory conditions
• Unrecognized persistent infection
• PD related
• Peritonitis
• Exposure to endotoxin or other cytokine inducing
  substance from contaminated dialysate

116
Proposed Features of Malnutrition Types
Stenvinkel P, et al. Nephrol Dial Transplant
200015953-60
Type 1 Type 2
Serum albumin Normal/low low
Co-morbidity uncommon Common
Presence of inflammation No Yes
Food intake low Low/normal
REE Normal Elevated
Oxidative stress Increased Markedly increased
Protein catabolism decreased Increased
Reversed by dialysis or nutrition support yes no
117
Additional Causes of Malnutrition in CAPDFactors
not associated with mode of PD

• underdialysis/
• insufficient removal of low molecular wt toxin
• reduced residual renal function
• accumulation of middle molecules (1-5kdal)
  anorexia
• tastelesss of renal diet
• MA
• endocrine factors
• gastroparesis and delayed GET
• SE of medication
• infection
• comorbidity
• psychosocial factors
• low physical activity/advance age/long duration
  of dialysis

118
Causes of Malnutrition in CAPD Factors associated
with mode of PD

• aa (1.2-3.4 g/d), vitamin, protein loss (5-15
  g/d) loss of protein up to 50-100 when
  peritonitis
• glucose absorption suppress appetite
• subjective feeling of fullness
• cytokine release less than HD
• peritoneal transport type high peritoneal
  transport rate

119
nPCR

• UNA Urea nitrogen appearance. Measure of the
  total nitrogen per day removed from body
  (excreted dialyzed).
• nPCR PNA protein equivalent of nitrogen
  appearance.
• In steady-state, in out and nPCR UNA. UNA
  then provides a measure of protein intake.

120
nPCR and Kt/V

• Increasing Kt/V may increase nPCR as a
  mathematical artifice.
• Debatable that increasing Kt/V results in an
  increase in albumin or in dietary protein intake.

121
Effects of Nutritional Therapy on the Progression
of Renal Insufficiency

• Non diabetic
• Diabetic

122
Effects on Progresion of Renal Insufficiency
Non-Diabetic

• no definitively established whether protein
  restriction in CRF slow the progression of RF

Ziller K N Engl J Med 1991 32478. Ciavarella
et al 1987, Walker et al 1989, Dullaarr et al 1991
123
Modification of Diet in Renal Disease StudyLPD
vs. normal protein
124
Modification of Diet in Renal Disease StudyLPD
vs. normal protein
Klahr S. N Engl J Med 1994 330 877.
125
Modification of Diet in Renal Disease Study
126
The Effect of Dietary Protein Restriction on the
Progression of Diabetic Renal Disease LPD vs.
normal protein
Pedrini MT. Ann Int Med 1996 124 627.
127
Effects on Progression of Renal Insufficiency
Diabetic

• Diabetic nephropathy
• Protein restriction (0.6/kg/d) decreased
  proteinuria, slow worsening of renal failure
• Strong indication but non conclusive proof LPD is
  beneficial in type 1 DM
• Reduce nocturnal microalbuminuria, delayed onset
  or progression of DN. Esp in hyperfiltrating pts,
  independent of glycemic control in type1 DM

Ziller K N Engl J Med 1991 32478. Pedrini
MT. Ann Int Med 1996 124627. Zarazaga A.
Clin Nutr 2001 20 291.
128
The Effect of Dietary Protein Restriction on the
Progression of Non Diabetic Renal Disease LPD
vs. normal protein
Pedrini MT. Ann Int Med 1996 124 627.
129
Meta-analyses on effects of LPD
Diet (g/kg/d) Patients End Point Reduction
0.3-0.6 vs gt 0.6 89 ESRD, DEATH 46
0.4- 0.6 vs gt 0.8 1,413 ESRD, DEATH 33
0.5-0.8 vs 0.6-free diet 108 (DM) Decline in GFR 46
0.6 vs 1 1,919 Decline in GFR 0.53 ml/min/yr
0.3-0.6 vs gt 0.6 1,494 ESRD, DEATH 39
130
Effect on Nutritional Status A Systematic Review

• Good metabolic tolerance to protein restriction
  hyperglycemia, insulin requirement
• Anthropometric parameter preserved
• no change or slight improvement in albumin, TG,
  cholesterol
• conclusion LPD maintain and/or improved
  anthropometric, and biochem. in diabetic grade B
  recommendation

131
Management of Malnutrition

• Early
• Adequate dialysis
• enteral supplement
• intraperitoneal nutrition
• management of inflammation elevate CRP
• Anabolic factors

132
Strategies for Treating Malnutrition in CAPD

• Adequate dialysis
• Adequate rx of MA
• Anemia treatment
• Prevent infection
• Adequate protein/energy intake
• Avoid medication interfering food intake, GI
  function
• Oral supplement / EN
• If all fail, no improvement in status and no RRF,
  pt should be transferred to HD

133
Criteria for Malnutrition

• Albumin lt 4.0 g/dL
• decrease in EDW
• nPCRlt 0.8g/kg/day
• low Cr, BUN without RRF
• Decreased anthropometrics

• (IGF-1 lt 300 mg/L)
• low predialysis serum K and phos
• (prealbuminlt30 mg/dL)
• Tchol lt 150 md/dL
• TFN lt 150 mg/dL

(Wolfson, 1997)
134
Nutritional requirement in CRF (non dialysis)
ESPEN NKF
GFR 25-70 ml/min 0.55-0.6 (2/3 HBV)
GFR lt25 ml/min 0.55-0.6 (2/3 HBV) Or 0.28 EAA or EAAKA 0.6 Or 0.75 (intolerance or inadequate energy
Mineral requirement Mineral requirement
P 600-1000 mg
K 1500-2000 mg
Na 1.8-2.5 g
135
Nutritional requirement in CRF (non dialysis)
ESPEN NKF
Protein intake HD PD 1.2-1.4 (gt1/2 HBV) 1.2-1.5 (gt1/2 HBV) 1.2 (gt1/2 HBV) 1.2-1.3 (gt1/2 HBV)
Energy HD PD 35 lt60 35 lt60 30
Mineral requirement Mineral requirement
P 800-1000 mg
K 200-2500 mg
Na 1.8-2.5 g
136
Formula

• Standard
• Nephro formula high concentration, low in
  electrolytes

137

• Intensive care

138
Indication

• All pt who are not expected to be on a full oral
  diet within 3 d should receive EN
• Hemodynamically stable critically ill patients
  who have a functioning GI tract should be fed
  early (lt24hr) using an appropriate amount

139
Application

• No general amount can be recommended as EN,
  adjusted to progression/course of diseases and GI
  tolerance
• Exogenous energy
• Acute and initial phase of critical illness
• 20-25 kcal/kg/d
• During anabolic recovery phase
• 25-30 kcal/kg/d
• Severe undernutrition
• 25-30 kcal/kg/d
• Consider prokinetics in pt with intolerance

ESPEN Guideline on EN Intensive Care. Clin Nutr
2006
140
Route

• Use EN in pt who can be fed
• No significant diff between jejunal feed and
  gastric feed
• Use supplemental PN in pt who cannot be fed
  sufficiently

141
Formula

• Whole protein formula
• IMN
• Arginine
• Gluctamine
• Ribonucleic acid
• N-3 fatty acid
• In elective upper GI pt
• Mild sepsis (APACHEII lt15)
• Trauma
• ARDS formula containing n-3 FA

ESPEN Guideline on EN Intensive Care. Clin Nutr
2006
142
Formula

• No recommendation of IMN in
• Burned
• Severe sepsis (APACHEII gt 15)
• ICU pt cannot tolerate gt 700 ml receive IMN
• Glutamine should be added to standard EN in (A)
• Burned pt
• Trauma pt