Clinical Nutrition Support Have we got it all wrong ? Dr Mike Stroud FRCP Senior Lecturer in Medicine & Nutrition, Consultant Gastroenterologist Southampton.

Clinical Nutrition Support Have we got it all wrong ?

Dr Mike Stroud FRCPSenior Lecturer in Medicine & Nutrition,

Consultant GastroenterologistSouthampton

Apologies

• BSG talk because of NICE Guidelines

• NICE Guidelines 1st Draft

• Contention

40% of hospital patients are overtly malnourished on admission, 8% severely

Causes of Malnourishment

Conscious levelDepressionAnorexia

Poor diet - age, poverty, junk, exercise, alcohol

Dysphagia

ObstructionVomiting

Pancreatic failureLiver processing

Jaundice

Malabsorption

Increased Metabolic demands

Effects of Undernutrition

Immunity – Increased risk of infection

HypothermiaImpaired gutintegrity andimmunity

Renal function - loss of ability to excrete Na & H2O

Decreased Cardiac output

Ventilation - loss ofmuscle & hypoxic responses

Psychology –depression & apathy

Anorexia ? Micronutrient deficiency

Loss of strength

liver fatty change, functional declinenecrosis, fibrosis

Impaired wound healing

NUTRITIONAL SUPPORT SHOULD:

Improve general status Immunity Wound healing Ventilation MobilityPsychology

Feeding gives time for other medical and surgical interventions to work

ITU patients would die at 20 to 30 days

Make stronger for discharge

Southampton CNRD Team Meta-analyses of oral/enteral

nutrition support trials.

0 10 20 30 40 50 0 5 10 15 20 25 30

30 RCT, n = 3258RR 0.59 (CI 0.48 to 0.72)

10 RCT, n = 494; RR 0.29 (CI 0.18 to

0.47)

Decreased complication % Decreased mortality %

Controls Controls

Treatment Treatment

So why think we may be wrong ?

• Better understanding of the effects of starvation

• Problems in the evidence for Nutrition Support

UNDERNUTRITION: EFFECTS ON METABOLISM

Na/K pumping: -30%

Decreased AA transport

Decreased protein synthesis: -40%

Decreased glucose transport

Decrease in metabolic mass

Decreases in: GH Insulin ILGF1,2 Adrenaline NA Glucagon T4 & T3

Reduced physical activity

REDUCTIVE ADAPTATION

Changed metabolism

Reduced work, increased efficiency

Metabolically stable BUT loss of reserve and functional capacity

‘Marasmus’

Changed body composition

Reduced Mass

REDUCED FOOD INTAKE

MARASMUS - Metabolically stable reductive adaptation

Adult marasmus in anorexia nervosa

Albumin 42

REDUCTIVE ADAPTATIONDECOMPENSATION

Changed body composition Changed body composition

Reduced work, increased efficiency

Marasmus

Reduced Mass

REDUCED FOOD INTAKE

Infection, trauma, small bowel overgrowth, specific deficiency, abnormal losses, excessive intake, unbalanced intake

Loss of homeostasis ‘Kwashiorkor’

DECOMPENSATED UNDERNUTRITION: KWASHIORKOR

Variable loss of fat /muscle i.e. marasmus

Response to infection, injury, fluids, feeding

Massive salt and water retention +oedema

Depletion of K, Mg, Ca, P

Reduced intra-cellular GSH

Increased urinary loss of nitrate

Increased cytokines

Peroxidation of cell membranes

Leaky membranes

Loss of vascular proteins

Post-surgicalMetabolic decompensationAdult ‘Kwashiorkor’

Adult, post-surgicalOedematous malnutrition

Albumin = 16

Recovery from oedema Albumin = 18

Albumin before and after the resolution of Oedema

The Problems of EBM in Nutrition Support

– Trials use different • Indications for intervention AND EXCLUSION• Levels of feeding • Controls• Starting times• Routes of support• Duration of support• Outcome measures

The Evidence

Wanted – volunteers for randomized, placebo controlled trial

Patients with an undoubted need for nutrition support cannot be randomized

Nutrition Support and Death

• Recommendation:– You should not let your patients go without

any form of nutrition whatsoever for 3 months

Grade: GPP

Grade: IBO

Why does nutrition support help ? Jeejeebhoy KN.‘The benefits of nutritional support

are evident when too little nutrition is given for too short a time to have any noticeable influence on lean body mass or circulating proteins

2. Correction of micronutrients ? Many of the detrimental effects attributed to

undernourishment are more easily ascribable to micronutrient rather than macronutrient shortages.

Prevalence of Micronutrient DeficienciesNational Dietary and Nutrition Survey (1998)

DeficiencyFree Living >65 yr

% incidenceInstitution >65yr

% incidence

Folate 29 (8 severe) 35 (16 severe)

Thiamine 9 14

Vitamin B12 6 9

Vitamin D 2 5

Vitamin C 14 (5 severe) 40 (16 severe)

Sub-clinical deficiencyOptimal level

Impaired biochemical function

Functional deficiency Metabolic Immunological Cognition Work capacity

ClinicalDeficiency

Death

Plasma levels may be normal

Metabolic evidence that Vitamin B12, Folate & Vitamin B6 occur commonly in elderly people

Jorsten et al. Am J Clin Nutr 1993

Levels of homocysteine & other metabolites accumulate if B12, folate or B6 are deficient - better indicator of vitamin status

SUBJECTS 99 younger healthy controls (19 - 55) vs 64 healthy elderly (65 - 88) vs. 286 hospital patients (61 - 97)

Elevated levels reverted to young healthy levels with vitamin supplements

Healthy elderly Elderly patients

low B12 6% 12.5%

low folate 5% 19%

low B6 9% 51%

Raised metabolites 63% 83%

Substrate A

Product B

Vitamin X

Product C

Vitamin YSupplementation of Vitamin X can cause:Vitamin X toxicityShortage of Substrate AExcess of product B or CDeficiency of Vitamin Y

Supplementation and metabolism

Food First ??

3. Metabolic switching ? – 400g carbohydrate pre-op alters insulin

resistance and decreases post-operative L.O.S. by 20%*

*Nygren J, Thorell A, Ljungqvist O. Preoperative oral carbohydrate nutrition: an update.

Curr Opin Clin Nutr Metab Care. 2001; 4(4):255-259

Issues in Nutrition Support

WHEN ?

WHAT ?

HOW ?

WHY ?

Starvation & Weight loss(After Allison)

50

55

6065

70

75

80

8590

95

100

0 10 20 30 40 50 60 70

Catabolic

Complete starvation

Partial starvation

Decision Box%bodyweight

Days

MALNUTRITION AND THE CATABOLIC RESPONSE

METABOLIC

RATE

MALNUTRITION

Pre -existing malnourishment

Catabolism

Feeding

10 2030

Safe to FeedNeed to feedNo

Our nearest ancestor

Teleology n. the doctrine of the final causes of things: interpretation in terms of purpose (Oxford English Dictionary)

Teleology, anorexia and survival

• To ensure rest ( ? death) after injury

• Metabolic machinery is depleted, ‘broken’ or diverted – Micronutrient & electrolyte depletion– Inadequate hepatic processing – Diet contains incorrect substrates for acute phase response

Sequestration of ‘nutrients’ e.g. Iron

Issues in Nutrition Support

WHEN ?

WHAT ?

HOW ?

WHY ?

PREDICTING ENERGY REQUIREMENTS

Schofield/Harrison Bendict BMR+ 10% - 50% Stress+ Fever (10%/degree C)+ 10% Thermic effect of feeding

Activity-10% ventilated+10% lying in bed+20% Bed to chair+40% up around ward

Energy expenditure in patients

Predicted REEs (Schofield BMR + 30%)vs. Deltatrak measurements of REE

Measured REE - kcals/day

0

500

1000

1500

2000

2500

0 500 1000 1500 2000 2500 3000

Est

imat

ed R

EE

- k

cals

/day

Why are current recommendations 35 - 40 kCals/kg /day non-protein calories ?

Problems of overfeeding energy• Ventilatory demands - O2 and CO2

• Lipid – Liver dysfunction– Immunosuppression

• Carbohydrate– Re-feeding syndrome– Wernicke Korsakoff

– Hyper-glycaemia

THE REFEEDING SYNDROME

K

Na

Mg

PO4

+ abnormalities of renal salt and water handling

= acute circulatory failure and death

ATP

PENG Guidelines

• Check K, PO4, Phos if low check Mg

• Correct levels

• Thiamine

• 20 kcal/kg

• Monitor K, PO4, Ca (Mg if supplements were given)

Lynne 51

• 1 yr 45% wt loss ?pathology, ? Eating disorder

• Wt 35kg, BMI 15

• Na 137, K 2.5, PO4 0.54, Mg 0.8, Ca 3.3

Given 240 kcals/day via NG tubeIV fluids 2 l/24 hrThiamine, vitamin B co, K, PO4, Mg supplements

Lynne – cont’d

• Day 1 Day 2• Creat 166 110• Urea 15.5 11.4• K 2.5 3.4• Ca 3.0 2.37

PO4 0.54 0.17Mg 0.8 0.4

Intensive Insulin Therapy in Critically Ill Patients

Van den Berghe et al. NEJM 2001; 345:1359-1367.

• PRCT in 1548 adults on surgical ICU. Insulin to maintain glucose <6.0 mmol vs. insulin to maintain glucose <12 mmol

• Also reduced in-hospital mortality by 34%, bloodstream infections by 46%, ARF requiring haemofiltration by 41%.

0

5

10

15

20

25

ICU mortality ICU >5 daymortality

InsulinConventional

P<0.04

P<0.005

Peritonitis (animal model)

0

10

20

30

40

50

60

Survival @ 17 days

100kcal/kg/day125kcal/kg/day150kcal/kg/day175/kcal/kg/day

Peck et al 1989

Energy RequirementsInitial refeeding or ongoing "stress" - cover RMR (approx 20kcal/kg)Start slowly with generous micronutrient & intracellular electrolytes

Low threshold for giving insulin

Problems of overfeeding nitrogen ?

• Catabolism evolved for survival to provide AAs for immunity, inflammation and repair.

• AA demands are greater AND different to normal requirements.

• THEREFORE

• Diet/conventional nutritional support not only fails to meet AA needs but supply excess unwanted (toxic) AAs

Why are current recommendations 0.2 - 0.3g N/kg with higher levels for catabolic patients ?

The influence of Nitrogen intake on Nitrogen Balance

Severe injury/illness

• Current recommendations for nitrogen 0.2 - 0.3g N/kg with higher levels for catabolic patients

• Mainly based on improvements in nitrogen balance NOT outcome.

• Maintaining N balance with GH is harmful

• Studies of lower levels of feeding required

Peritonitis (animal model)

0

5

10

15

20

25

30

35

40

45

Survival @ 14 days

5% protein10% protein15% protein20% protein

Peck et al 1989

Collins et al. Am J Clin Nutr 1998

Somalia: relief camp during famine 92/93573 adults: 83 oedematous, 377 non-oedematousWeight 35 kg, BMI 13.1 kg/m2

Overall mortality 21% (oedematous 37%)

Low protein (8.5%) High protein (16.4%)

Mortality 14/52 14/27

Appetite better poor

Oedema -7.2 g/kg/d + 6.3 g/kg/d

NUTRITIONAL SUPPORT Go for Balance

MACRONUTRIENTSProteinCarbohydrate Fat

MICRONUTRIENTSFat soluble - A, D, E, KWater soluble - B Group, C, etc

ELECTROLYTESNa, K, Ca, MgPhosphate

ELEMENTSIron

Zn, Se, Cu, Mn

NUTRITIONAL SUPPORT

MAINTAINREPAIR REPLETE

Issues in Nutrition Support

WHEN ?

WHAT ?

HOW ?

WHY ?

MEETING PATIENTS NUTRITIONAL NEEDS

NORMALLY NOURISHEDUndernourished

BMI<20Wt Loss >10%

IF

ASSESSMENT - Ward staff

PROVISION - Catering

MONITORING - Admission & weekly wt

Partial IF

ASSESSMENT - Nutrition support team PROVISION - Pharmacy PN via +/- enteral

or oral

ACCESS - CVP or peripheral line

MONITORING - Daily reassessment including intake, fluid balance and biochemistry + weekly wt

ASSESSMENT - Ward Staff & dietitians

PROVISION - Catering +/- oral supplements

MONITORING - Admission & weekly wt + intake records + biochemistry

ASSESSMENT- Dietitians & Ward staff +/- NST

PROVISION - Pharmacy enteral feeds +/- catering and sip feeds

ACCESS - via NG, NJ, PEG

MONITORING - At least 2 x weekly clinical reassessment + weekly wt + intake records + biochemistry

Parenteral nutrition

Total parenteral nutrition in the critically ill patient – A meta analysis.

Heyland et al. JAMA 280, 1998

• 26 RCTs in 2211 surgical and ICU patients compared TPN vs standard care.

• NO effect on mortality

• NO effect on complication rate

• Potentially dangerous in ICU patients

• Why ?

Problems with PN studies • Subject selection excludes patients requiring PN

• Control groups receive PN when patients develop prolonged ileus or other persisting gut dysfunction (USA Veterans PN trial 13% of controls received PN).

• Overfeeding (nearly all patients hyperglycaemic)

• PN studies therefore reflect – effects of PN performed badly in patients who don’t need it.

PN – The 7 day myth

Are enteral vs. PN studies valid ?• Repeated studies show benefits of enteral vs. PN

feeding.• BUT• Enteral feeding is almost always limited in sick

patients• THEREFORE• all studies compare different routes AND different

levels of early feeding. – e.g. Meta-analyses in pancreatitis patients shows no

advantage of EN vs. PN if hyperglycaemic patients left out.

Enteral versus parenteral nutrition: a pragmatic study.

Woodcock et al. Nutrition 2001;17(1):1-12. • Clinicians’ assessed GI function in 562 patients needing support. 231

ETF; 267 PN; 64 randomised ETF or PN

– adequate nutrition in randomised patients 22% ETF vs. 75% PN (p< 0.001).

– No differences in sepsis rates between groups

– Feeding complications more frequent in elective and randomised ETF patients.

– Higher mortality in both non-randomised and non randomised ETF groups.

THE SOUTHAMPTON COURSE IN PRACTICAL

NUTRITIONAL SUPPORT

Sep 2006

Course Directors: Brendan Moran - Consultant SurgeonMike Stroud - Consultant Physician