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

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 level Poor diet - age, poverty, junk, Depression exercise, alcohol Anorexia Dysphagia Obstruction Vomiting Pancreatic failure Liver processing Jaundice Malabsorption Increased Metabolic demands

Effects of Undernutrition Psychology – depression & apathy Ventilation - loss of muscle & hypoxic responses Immunity – Increased risk of infection liver fatty change, functional decline necrosis, fibrosis Decreased Cardiac output Renal function - loss of ability to excrete Na & H2O Impaired wound healing Hypothermia Impaired gut integrity and immunity Loss of strength Anorexia ? Micronutrient deficiency

NUTRITIONAL SUPPORT SHOULD: Improve general status Immunity Wound healing Ventilation Mobility Psychology

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. 10 RCT, n = 494; RR 0.29 (CI 0.18 to 0.47) 30 RCT, n = 3258 RR 0.59 (CI 0.48 to 0.72) Controls Controls Treatment Treatment Decreased complication % Decreased mortality %

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 Reduced physical activity Decrease in metabolic mass Decreased protein Na/K synthesis: -40% pumping: -30% Decreased Decreased glucose transport AA transport Decreases in: GH Insulin ILGF1,2 Adrenaline NA Glucagon T4 & T3

Metabolically stable BUT loss of reserve and functional capacity REDUCTIVE ADAPTATION REDUCED FOOD INTAKE Changed body composition Reduced Mass Changed metabolism Reduced work, increased efficiency Metabolically stable BUT loss of reserve and functional capacity ‘Marasmus’

MARASMUS - Metabolically stable reductive adaptation

Adult marasmus in anorexia nervosa Albumin 42

REDUCTIVE ADAPTATION DECOMPENSATION REDUCED FOOD INTAKE Reduced work, increased efficiency Reduced Mass Changed body composition Changed body composition Marasmus Infection, trauma, small bowel overgrowth, specific deficiency, abnormal losses, excessive intake, unbalanced intake Loss of homeostasis ‘Kwashiorkor’

DECOMPENSATED UNDERNUTRITION: KWASHIORKOR Response to infection, injury, fluids, feeding Reduced intra-cellular GSH Depletion of K, Mg, Ca, P Increased urinary loss of nitrate Increased cytokines Variable loss of fat /muscle Peroxidation of cell membranes i.e. marasmus Massive salt and water retention +oedema Leaky membranes Loss of vascular proteins

Post-surgical Metabolic decompensation Adult ‘Kwashiorkor’

Adult, post-surgical Oedematous 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

Wanted – volunteers for randomized, placebo controlled trial 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 Deficiencies National Dietary and Nutrition Survey (1998) Free Living >65 yr Institution >65yr Deficiency % incidence % 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 deficiency Optimal level Impaired biochemical function Plasma levels may be normal Functional deficiency Metabolic Immunological Cognition Work capacity Clinical Deficiency Death

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) Healthy elderly Elderly patients low B12 6% 12.5% low folate 5% 19% low B6 9% 51% Raised metabolites 63% 83% Elevated levels reverted to young healthy levels with vitamin supplements

Supplementation and metabolism Vitamin X Substrate A Product B Supplementation of Vitamin X can cause: Vitamin X toxicity Shortage of Substrate A Excess of product B or C Deficiency of Vitamin Y Vitamin Y Product C

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 WHY ? WHEN ? WHAT ? HOW ?

Starvation & Weight loss (After Allison) % 50 55 60 65 70 75 80 85 90 95 100 10 20 30 40 Catabolic Complete starvation Partial starvation b Decision Box o d y w e i g h t Days

MALNUTRITION AND THE CATABOLIC RESPONSE Pre -existing malnourishment Catabolism MALNUTRITION METABOLIC RATE Feeding 30 10 20 No Need to feed Safe to Feed

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 Sequestration of ‘nutrients’ e.g. Iron Metabolic machinery is depleted, ‘broken’ or diverted Micronutrient & electrolyte depletion Inadequate hepatic processing Diet contains incorrect substrates for acute phase response

Issues in Nutrition Support WHY ? WHEN ? WHAT ? HOW ?

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 2500 500 1000 2000 Predicted REEs (Schofield BMR + 30%) Estimated REE - kcals/day vs. Deltatrak measurements of REE 1500 500 1000 1500 2000 2500 3000 Measured REE - kcals/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 Mg + abnormalities of renal salt and water handling K = acute circulatory failure and death Na PO4 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 tube IV fluids 2 l/24 hr Thiamine, 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 0.17 Mg 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%. P<0.005 P<0.04

Peritonitis (animal model) Peck et al 1989

Energy Requirements Initial 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 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) Peck et al 1989

Collins et al. Am J Clin Nutr 1998 Somalia: relief camp during famine 92/93 573 adults: 83 oedematous, 377 non-oedematous Weight 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 MACRONUTRIENTS Protein Carbohydrate Fat MICRONUTRIENTS Fat soluble - A, D, E, K Water soluble - B Group, C, etc ELECTROLYTES Na, K, Ca, Mg Phosphate ELEMENTS Iron Zn, Se, Cu, Mn

NUTRITIONAL SUPPORT MAINTAIN REPAIR REPLETE

Issues in Nutrition Support WHY ? WHEN ? WHAT ? HOW ?

MEETING PATIENTS NUTRITIONAL NEEDS 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 ASSESSMENT - Ward staff PROVISION - Catering MONITORING - Admission & weekly wt NORMALLY NOURISHED Undernourished BMI<20 Wt Loss >10% Partial IF IF ASSESSMENT - Ward Staff & dietitians PROVISION - Catering +/- oral supplements MONITORING - Admission & weekly wt + intake records + biochemistry 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

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 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 Surgeon Mike Stroud - Consultant Physician