Case approach in nutrition support October 2005

Preyanuj Yamwong Research Center for Nutrition Support, Siriraj Hospital

What you should know in clinical nutrition Nutritional assessment Nutrients deficiency : Protein, energy, vitamins, minerals (Macro/trace elements) Over Nutrition : Obesity, Dyslipidemia, Vitamin & minerals excess Nutrition support : EN, PN, Nutrition support in specific diseases Nutrition and disease prevention/modification Functional food

Case 1 67 BS 180 mg/dL

Route of nutritional support Energy requirement Protein requirement Type of protein

Glucose and Insulin after Preop. and Postop. Glucose Infusion Tests

25 20 15
GLUCOSE p (mmol/L)

Glucose IRI

240 200 160 120

10 5 0
MINUTES GITest

IRI

80 mU/L 40 0

30

60

90

30

60

90

PREOPERATIVE

POSTOPERATIVE Giddings et al. Ann Surg 1977;186:681-686

Intensive Insulin Therapy

CONVENTIONAL

INTENSIVE

Morning BS mg/dl

173

103

Insulin dose U/day

33

71

Van den Berghe et al. 2001

Cumulative Survival of Patients under Conventional vs. Intensive Insulin Therapy In ICU

SURVIVAL IN ICU (%)

100 96 92 88 84 80

HOSPITAL SURVIVAL (%)

100 96

Intensive insulin

Intensive insulin Conventional insulin

92 88 84 80

Conventional insulin
50 100 150 200 250

20 40 60 80 100 120 140 160 DAYS AFTER ADMISSION

DAYS AFTER ADMISSION

Van den Berghe et al, 2001

Effects on Morbidity of Intensive Insulin Treatment on Critically Ill Patients

VARIABLE >14 days of IC (%) >14 days ventilatory support (%) Septicemia (%) Antibiotics >10 days (%) Polineuropathy at any time (%)

CONVENTIONA L TREATMENT

INTENSIVE TREATMENT

P VALUE

15.7 11.9 7.8 17.1 51.9

11.4 7.5 4.2 11.2 28.7

0.01 0.003 0.003 <0.001

<0.001

Van der Berghe et al, 2001

Is Strict Normoglycemia Necessary ?

Cumulative Hazard (%) (in hospital death)

Patients in ICU for > 5 days (N = 451)

45

p = 0.0009
40 35 30 25 20 15 10 5
0 0 50 100 150 200 250

> 150 mg / dl 110-150 mg / dl < 110 mg / dl p = 0.026

Days after inclusion

Van den Berghe G et al. Crit Care Med 2003; 31: 359-366

Diabetes mellitus and stress induced hyperglycemia

Most common pathogenesis : insulin resistance Enteral formula

addition of dietary fiber may improve glycemic control High monounsaturated fatty acids may also improve glycemic control Feeding frequency depends on type of insulin used

Parenteral nutrition

Addition of insulin in glucose bottle or dripping parallel to glucose Follow up TG as well as glucose

Blood Glucose Response to Standard and Disease Specific Enteral Formulas in Type 1 Diabetes
Blood glucose (mg/dL)

300 250 200 150 100 50 Standard 0 -30 0 30 60 90 120 150 180 210 240
Peters A et al, Am J Med 1989 Time (Minutes)

Disease specific

Blood Glucose Responses to Diabetes-specific and Standard Enteral Formula in Stress-induced Hyperglycemia
Blood glucose (mg/dL) 300
250 200 150 100 50 Standard 0 0 1 2 3 4 5 6 7 Diabetes-specific

Day Coulston AM, Clin Nutr 1998

Diabetic Formula
Commercial formula
Glucerna Glucerna SR Choice DM

Blenderized diet
Change composition of glucose to fructose or starch Reduce fat composition

Since this patient has high stress, is there any rational to use Glutamine and other immuno-nutritions?

Nutrients with Immuno-modulating Properties Amino acids

Glutamine Arginine

Fat
Omega-3 fatty acids

Others
Nucleotides (RNA)

Arginine

NH3+

H3+N-C-NH-CH2-CH2-CH2-C-COONH H

Conditionally essential amino acids Stimulate the secretion of GH, insulin, insulin-like growth factor-1, prolactin Precursor of Nitric oxide (NO)

Arginine Supplementation
protein breakdown nitrogen retention Promote wound healing tumor growth lymphocyte proliferation activity of NK, lymphokine activated killer cells phagocytic activity of neutrophil

Glutamine

NH3+

NH3+

H2N-C-CH2-CH2-C-COO Most abundant amino acids Conditionally essential amino acids Substrate for hepatic gluconeogenesis Precursor of nucleotides, glutathione Energy source of enterocytes, rapidly mitotic cells eg. immune cells H

Glutamine Supplementation

protein synthesis hepatic gluconeogenesis nitrogen retention Maintain small bowel mucosal thickness and prevent villi atrophy

Diet Linolenate -Linolenate Eicosatrienoate

(dihomo---Linolenate)

Group 2 Group 1
PGE1 PGF1 TXA1 LTA3 LTC3 LTD3 PGD2 PGE2 PGF2 PGI2 TXA2 LTA4 LTB4 LTC4 LTD4 LTE4

Eicosatrienoate Arachidonate Group 3

PGD3 PGE3 PGF3 PGI3 TXA3 LTA5 LTB5 LTC5

Octadecatetraenoate Eicosatetraenoate -Linolenate Diet Eicosapentaenoate Diet

Reduced Postoperative Infections with an Immuneenhancing Nutritional Supplement

70

Number of infections

60 50 40 30 20 10 0-

Wound Pulmonary Intestinal Urinary Other None

Immunonutrition Standard enteral formula (n = 47) (n = 82) Synderman CH, et al 1999

Prospective DBRCT of Enteral Immunonutrition in the Critically Ill

Days
20 18 16 14 12 10 8 6 4 2 0

p = 0.03

p = 0.007
Immunonutrition Standard enteral formula

Ventilation

Hospital stay

Atkinson S, et al Crit Care Med 1998

Early Enteral Administration of a Formula Supplemented with Arginine, Nucleotides and Fish Oil in Intensive Care Unit Patients
Length of hospital stay (day)
120 100 80 60 40 20 0 Regular formula Supplemented formula

0 0

0 1

1 1

0 3

1 3

0 5

1 Inc. of post-feeding inf. 5 No. of acquired inf.

Early Enteral Administration of a Formula Supplemented with Arginine, Nucleotides and Fish Oil in ICU Patients (Multicenter, Perspective, RCT)
Number of days in hospital stay/ Number of patients with acquired infection

Clinical outcome in successful feeders

30

p < 0.05
25 20 15 10 5 0 Hospital stay UTI Bacteremia Immunonutrition Standard enteral formula

Bower RH, et al Crit Care Med 1995

Early Post-operative Enteral Immunonutrition: Clinical Outcome and Cost-comparison Analysis in Surgical Nutrition
German Marks (000s)
140 120 100 80 60 40 20 0 Early complication Total cost 52.6 47.8 31 74.6 83.6 Immunonutrition Standard enteral formua 122.4

Senkel M, et al Crit Care Med 1997

Outcome and Cost-effectiveness of Perioperative Enteral Immunonutrition in Patients Undergoing Elective Upper GI Surgery
German Marks (000s)
250 200 150 100 50 0
Early Late complication complication Total

Immunonutrition Standard enteral formula

Senkel M, et al Arch Surg 1999

Six-month outcome of critically ill patients given Glutaminesupplemented parenteral nutrition

Griffiths RD, et al . Nutr 1997;13:295-302

Available Immunonutrition Formula

Neomune : high protein (64 g/1000 kcal), with Glutamine and fish oil Dipeptiven : dipeptide contains glutamine

Since this patient has respiratory failure, does he need fat modification diet?

Respiratory quotient (RQ)

O2 consumption while metabolizing CO2 production certain amount of nutrient C6H12O6 + 6O2 6CO2 + 6H2O

EN in Respiratory Failure The major concern is about CO2 overproduction which can precipitate respiratory failure or compromise weaning CO2 induced respiratory failure were reported in COPD cases who received more than 2,000 kcal from CHO per day Usually patients with respiratory failure are in hypercatabolic state and require higher energy and protein

EN in Respiratory Failure Not all patients with respiratory failure need high fat formula AGA may be necessary to monitor the over-production of CO2 if high energy is provided In cases who high fat formula is indicated the available formula is Pulmocare, Respalor, or modified BD

Available high fat formula

Pulmocare Respalor Addition of oils in standard feeding formula

If the patient develops acute renal failure after a week of treatment, how would you provide the nutrition support for him?
Nutrients provided and restricted? Route? Formula?

Metabolic Derangement in ARF

Hypermetabolism and hypercatabolism Influenced more by the nature of the illness Accumulation of metabolic products causing ARF Acidemia Underlying hypercatabolic condition Increase certain catabolic hormone (glucagon & PTH) due to ARF itself Poor dietary intake

Metabolic Derangement in ARF

Hypermetabolism and hypercatabolism Glucose intolerance : insulin resistance Protein and amino acids abnormalities : protein catabolism, azotemia Influenced more by the nature of the illness causing ARF

Protein Catabolism in ARF

Average UNA
12+7.9 g/D in patients with rhabdomyolysis vs. 3.8+2.4 g/D in ARF from other causes
Feinstein EI, et al, 1981

Net protein degradation 200-250 g/D

Feinstein EI, et al, 1983 Leonard CD, et al, 1975

Metabolic Derangement in ARF

Hypermetabolism and hypercatabolism Glucose intolerance : insulin resistance Protein and amino acids abnormalities : protein catabolism, azotemia Lipid metabolism : hypertriglyceridemia Acid-base disturbance : metabolic acidosis Fluid imbalance : hyper- / hypovolumia Electrolytes imbalance :hyper- / hyponatremia, hyper- / hypokalemia, hyperphosphatemia, hypocalcemia

 Metabolic abnormalities in patients with ARF differ from one case to another. In the same patient, the abnormalities can change from day to day or even hour to hour.

Nutrients Requirement and Limitation

Goals : Energy Protein

30-35 Kcal/Kg/D 1.5-2 g/Kg/d

Potential nutrients restriction in early phase - Water - Potassium - Sodium - Phosphate

Renal Replacement Therapy

Intermittent hemodialysis Continuous AV / VV hemodialysis (CAVHD, CVVHD) Peritoneal dialysis

Renal Repalcement Therapy and Its Impact on Nutritional Support

Acute peritoneal dialysis Continuous peritoneal dialysis loss of protein 5-9 gm/D in dialysate, glucose absorbed from dialysate Hemodialysis Loss of amino acids 6-9 gm/dialysis Increase energy expenditure during dialysis Continuous hemodiafiltration (VV, AV) Glucose absorbed from dialysate (5.8 gm./Hr for 1.5% glucose 1 L/Hr.) loss of amino acids ~13-24 gm. /D

Daily Recommendation of Patients with ARF

ARF (GFR 5-10) non stress Protein/AA (g/kg/d) Energy (kcal/kg/d) Fat (% of total energy) Water 0.55-0.6 of mixed AA 30-45 ARF HD 3/wk CVVH / CVVHD CAVH high stress ARF 1.5-2.5 of mixed AA 30-45

1.2 of mixed AA 30-45

20-30 20-30 20-30 (-- --- --- --- -- if not sepsis -- --- --- --- --- --) --- --- --- --- --- as tolerate --- --- --- --- --- -ASPEN Guidelines 2001

Feeding Formula
Preferred concentrated, low Na & low K formula Protein content depends on the status : pre-, post dialysis
High protein for post dialysis : Nepro Low protein for pre-dialysis : Prosobee, Pregestimil

Intravenous formula
Renal formula : ~ 60% of EAA is necessary when less than 40 g/day of AA are provided Formula : Kidmin, Nephrosteril, Amiyu

Assessment of Adequacy of Nutrition Support

Energy : Dry weight Protein : Serum albumin : Urea Nitrogen Appearance (UNA)
UNA (gm/D) = UUN + 0.6BWi (BUNf-BUNi) + BUNf (BWf-BWi)

: Total Nitrogen Appearance (TNA)

TNA (gm/D) = 1.27 + 1.19UNA

In conclusion, how you are going to feed this patient?

Priority Setting is the key!

Case 2
18 96 . 159 .
BMI = 96/(1.59)2 = 37.97 kg/m2

Body mass index for Asian people Grading Underweight Normal pre-obese Obese gr. 1 Obese gr. 2 BMI (Kg/m2) < 18.5 18.5 - 22.99 23.0 - 24.99 25.0 - 29.99 > 30.0

Obesity : Definition
Ideal body weight :
overweight > 110% of ideal body weight Obese > 120% of ideal body weight (Female : height [cm] 110, Male : height [cm] 100) Percent of body fat : > 30 in female, > 20% in male

Obesity : Definition
Waist circumference : BMI (Kg/m2)
> 25 > 30

Waist circumference
male 94 cm./ 37 female 80 cm. / 31 male 102 cm./ 40 female 88 cm. / 35

90 cm 94 cm

80 cm 80 cm

Morbid Obesity
BMI > 35 kg/m2 or obesity associated with severe/cardiovascular complications

Pear shape/Gynoid type

Apple shape/Android

Waist / hip ratio that reflects higher risk of CAD Women > 0.8 Men > 1,

 18 96 . 159 . 75 . ? ?

Obesity : complications
Metabolic complications (Waist > 100 cm in
male, > 90 cm in female) insulin resistance & diabetes Dyslipidemia Acanthosis nigricans Hypertension

Cardiovascular disease
coronary artery disease

Other endocrinological complication :

Amenorrhea (Polycystic ovarian syndrome)

Obesity : complications

Mechanical effects :

Joint : ankle joint, knee joint, back pain Respiration : sleep apnea syndrome fungal infection, varicose vein breast, endometrium, prostate, esophagus

Skin :

Cancer :

Gall stone Social & psychological problems


/ /

//
DM HT Allergy Depressive illness Schizophrenia Seizure OSA Polycystic ovarian syndrome Hypothyroidism Stress & anxiety Sulfonylurea Beta-blocker Antihistamine Antidepressant, Li Antipsychotic drugs

Transquilizer Contraceptive pills

Obesity : Management
Diet control Exercise & increase physical activity Behavioral modification Drug therapy Surgery

Weight loss in the Diabetes Prevention Program

Weight loss (kg)
4 2 0 -2 -4 -6 -8 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 Placebo Metformin Lifestyle

Year
DPP. N Engl J Med. 2002; 346: 393-403

Diabetes Prevention Program

40 Placebo RR* 31% RR* 58%

Cumulative incidence of diabetes (%)

30

Metformin

20

Lifestyle

10

0 0 0.5 1.0 1.5 2.0 2.5 Year 3.0 3.5 4.0

*Reduction in risk of progressing to type 2 diabetes versus placebo DPP.N Engl J Med. 2002; 346: 393-403

 /?
Diet Activity BMI 23-25 no risk Increase WC DM/CAD/HT/HL BMI 25-30 no risk Increase WC DM/CAD/HT/HL BMI > 30 no risk Increase WC DM/CAD/HT/HL Drug VLCD X X (consider) (consider) (consider) Surgery

Orlistat (Xenical) Action : inhibitor of pancreatic lipase : reduces fat absorption about 30% Effect : Weight reduction -9.2% vs. 5.8% after 2 yr. : Weight reduction > 10% : 42.1% vs. 22.7% after 2 yr. : Reducing LDL-C, TG : Improvement of glycemic control

XENDOS results
: Effect of Xenical on body weight

Change in weight (kg)

Placebo + lifestyle

Xenical + lifestyle

0 -3 -6 -9 -12 0 52 104 156 208

-4.1 kg -6.9 kg p<0.001 vs placebo

Week
Sjostrom et al. 9th ICO, Sao Paulo 2002. Poster Presentation

 Sibutramine (Reductil) Action : inhibition of re-uptake of serotonin and nor-epinephrine : resulting in prolonged satiety rather than anorectic effect Effect : Reduce BW, waist circumference, serum lipid levels Side-effect : may increase BP and HR in some cases : constipation : dry mouth : insomnia : no fenfluramine-like adverse effect

Effect of Sibutramine on weight maintenance after weight loss : a RT

The STORM Study Group, Lancet 2000, 2119-25

Case 3 35 1 tenderness & guarding epigastric area U/S diffuse enlargement of pancrease Serum amylase 1234 IU/L severity APACHE score moderate to severe pancreatitis

 Acute pancreatitis : oral/gastric stimulation of pancrease should be avoid Acute pancreatitis

Total Parenteral Nutrition

Enteral feeding

Stimulation of pancreatic enzyme secretion with various type of nutrient & site of feeding Stimulation of pancreatic exocrine secretion were similar by both intragastric and intraduodenal feeding Jejunal feeding did not associate with increase pancreatic enzyme and bicarbonate secretion Feeding of fat cause more secretion of pancreatic enzyme than feeding of CHO Amount of protein feeding (10% to 40% of total calories) was not associate with different enzyme secretion

Volume of pancreatic juice during enteral and total parenteral feeding

TEN

TPN Bodogy G, et al 1991, Am J Surg

Comparison of the safety of early enteral vs parenteral nutrition in mild acute pancreatitis Serum lipase Serum amylase
600 500 400 300 200 100 06000 5000 4000 3000 2000 1000 01 2 3 4 5 6 7 8 9 10

TEN TPN

Time

Time

1 2 3 4 5 6 7 8 9 10

McClave SA, et al. 1997 JPEN

 Acute pancreatitis : oral/gastric stimulation of pancreas should be avoid Acute pancreatitis Total Parenteral Nutrition
- Hyperglycemia - Catheter related sepsis - IV fat ?

Enteral feeding
- Use elemental diet, drip continuously - Jejunal tube beyond ligament of Treitz Nasojejunostomy under endoscopy Intraoperative tube placement