Clinical Nutrition Support Have we got it all wrong ?

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

2. Apologies • BSG talk because of NICE Guidelines • NICE Guidelines 1st Draft • Contention

3. 40% of hospital patients are overtly malnourished on admission, 8% severely

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

5. Effects of Undernutrition Psychology – depression & apathy Ventilation - loss of muscle & hypoxic responses Immunity – Increased risk of infection liver fatty change, functional declinenecrosis, 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

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

7. Feeding gives time for other medical and surgical interventions to work ITU patients would die at 20 to 30 days Make stronger for discharge

8. 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 %

9. So why think we may be wrong ? • Better understanding of the effects of starvation • Problems in the evidence for Nutrition Support

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

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

12. MARASMUS - Metabolically stable reductive adaptation

13. Adult marasmus in anorexia nervosa Albumin 42

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

15. 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

16. Post-surgical Metabolic decompensation Adult ‘Kwashiorkor’

18. Adult, post-surgical Oedematous malnutrition Albumin = 16

19. Recovery from oedema Albumin = 18

20. Albumin before and after the resolution of Oedema

21. 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

22. The Evidence Wanted – volunteers for randomized, placebo controlled trial Patients with an undoubted need for nutrition support cannot be randomized

23. 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

24. 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

25. 2. Correction of micronutrients ? Many of the detrimental effects attributed to undernourishment are more easily ascribable to micronutrient rather than macronutrient shortages.

26. 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)

27. Sub-clinical deficiency Optimal level Impaired biochemical function Plasma levels may be normal Functional deficiency Metabolic Immunological Cognition Work capacity Clinical Deficiency Death

28. 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

29. 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

30. Food First ??

31. 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

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

33. 100 95 90 85 80 Catabolic 75 Complete starvation 70 Partial starvation 65 60 55 50 0 10 20 30 40 50 60 70 Starvation & Weight loss (After Allison) % Decision Box b o d y w e i g h t Days

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

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

36. 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

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

38. 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

39. 1000 500 0 Energy expenditure in patients 2500 2000 Predicted REEs (Schofield BMR + 30%) Estimated REE - kcals/day vs. Deltatrak measurements of REE 1500 0 500 1000 1500 2000 2500 3000 Measured REE - kcals/day Why are current recommendations 35 - 40 kCals/kg /day non-protein calories ?

40. Problems of overfeeding energy • Ventilatory demands - O2 and CO2 • Lipid • Liver dysfunction • Immunosuppression • Carbohydrate • Re-feeding syndrome • Wernicke Korsakoff • Hyper-glycaemia

41. THE REFEEDING SYNDROME Mg + abnormalities of renal salt and water handling K = acute circulatory failure and death Na PO4 ATP

42. 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)

43. 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

44. Lynne – cont’d • Day 1Day 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

45. Intensive Insulin Therapy in Critically Ill PatientsVan 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

46. Peritonitis (animal model) Peck et al 1989

47. Energy Requirements Initial refeeding or ongoing "stress" - cover RMR (approx 20kcal/kg) Start slowly with generous micronutrient & intracellular electrolytes Low threshold for giving insulin

48. 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 ?

49. The influence of Nitrogen intake on Nitrogen Balance Severe injury/ illness

50. 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