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Nutritional Support in Critical Care Dr. Gwynne Jones University of Ottawa and the Ottawa Hospital.

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1 Nutritional Support in Critical Care Dr. Gwynne Jones University of Ottawa and the Ottawa Hospital.

2 Nutrition: Metabolic Profiles

3 Objectives 1. Evidence for Feeding 2. Metabolic Alterations in Critical Illness 1.Hypermetabolism/Hypercatabolism. 2.Energy expenditure/Fuel Requirements. 3.Carbohydrate and Sugar Control. 4.Lipids and Free Fatty Acids. 3. The Gut. 4. Immunonutrition. 5. Refeeding syndrome

4 Nutrition: Metabolic Profiles A 55 yr old man with Group A Streptococcal Septic Shock and Necrotising Fasciitis of the thigh is sedated and fully ventilated. He is receiving much fluid, pressors and stress dose steroids. His Lactate level is 10mMol/L. A 55 yr old man with Group A Streptococcal Septic Shock and Necrotising Fasciitis of the thigh is sedated and fully ventilated. He is receiving much fluid, pressors and stress dose steroids. His Lactate level is 10mMol/L.

5 Nutrition: Metabolic Profiles A 55 yr old man with Group A Streptococcal Septic Shock and Necrotising Fasciitis of the thigh is sedated and fully ventilated. He is receiving much fluid, pressors and stress dose steroids. His Lactate level is 10mMol/L. A 55 yr old man with Group A Streptococcal Septic Shock and Necrotising Fasciitis of the thigh is sedated and fully ventilated. He is receiving much fluid, pressors and stress dose steroids. His Lactate level is 10mMol/L. Would you feed this man now? Would you feed this man now?

6 Nutrition: Metabolic Profiles Caloric need during illness How many Calories would you feed this man? How many Calories would you feed this man?

7 Nutrition: Metabolic Profiles Caloric need during illness How many Calories would you feed this man? How many Calories would you feed this man? –1. 15 K.cal/Kg/Day –2. 20 K.cal/Kg/Day –3. 25 K.cal/Kg/Day –4. 30 K.cal/Kg/Day –5. 40 K.cal/Kg/Day

8 Nutrition: Metabolic Profiles Caloric need during illness How many Calories would you feed this man? How many Calories would you feed this man? In 1997 the American College of Chest Physicians (ACCP) issued a set of nutritional guidelines to reduce the variation in practice. Cerra and colleagues recommended in these guidelines that administering 25 total kilocalories per kilogram usual body weight per day appears to be adequate for most patients. In 1997 the American College of Chest Physicians (ACCP) issued a set of nutritional guidelines to reduce the variation in practice. Cerra and colleagues recommended in these guidelines that administering 25 total kilocalories per kilogram usual body weight per day appears to be adequate for most patients.

9 Nutrition: Metabolic Profiles A 55 yr old man with Group A Streptococcal Septic Shock and Necrotising Fasciitis of the thigh is sedated and fully ventilated. He is receiving much fluid, pressors and stress dose steroids. His Lactate level is 10mMol/L. A 55 yr old man with Group A Streptococcal Septic Shock and Necrotising Fasciitis of the thigh is sedated and fully ventilated. He is receiving much fluid, pressors and stress dose steroids. His Lactate level is 10mMol/L. How much Protein would you feed this man? How much Protein would you feed this man?

10 Nutrition: Metabolic Profiles A 55 yr old man with Group A Streptococcal Septic Shock and Necrotising Fasciitis of the thigh is sedated and fully ventilated. He is receiving much fluid, pressors and stress dose steroids. His Lactate level is 10mMol/L. A 55 yr old man with Group A Streptococcal Septic Shock and Necrotising Fasciitis of the thigh is sedated and fully ventilated. He is receiving much fluid, pressors and stress dose steroids. His Lactate level is 10mMol/L. How much Protein would you feed this man? How much Protein would you feed this man? – Gm Protein?Kg./Day – Gm Protein?Kg./Day – Gm Protein?Kg./Day – Gm Protein?Kg./Day – Gm Protein?Kg./Day

11 Nutrition: Metabolic Profiles A 55 yr old man with Group A Streptococcal Septic Shock and Necrotising Fasciitis of the thigh is sedated and fully ventilated. He is receiving much fluid, pressors and stress dose steroids. His Lactate level is 10mMol/L. A 55 yr old man with Group A Streptococcal Septic Shock and Necrotising Fasciitis of the thigh is sedated and fully ventilated. He is receiving much fluid, pressors and stress dose steroids. His Lactate level is 10mMol/L. They measured body composition by in-vivo electron analysis. They measured body composition by in-vivo electron analysis. Feeding more than 25KCal/Kg/day and 1.5G Amino Acids/Kg/day only succeeded in increasing fat deposition without increase in protein anabolism. Feeding more than 25KCal/Kg/day and 1.5G Amino Acids/Kg/day only succeeded in increasing fat deposition without increase in protein anabolism. Protein Requirements in Critical Illness. Streat et al. (J.Trauma1987;27: ) Streat et al. (J.Trauma1987;27: )

12 Nutrition: Metabolic Profiles A 55 yr old man with Group A Streptococcal Septic Shock and Necrotising Fasciitis of the thigh is sedated and fully ventilated. He is receiving much fluid, pressors and stress dose steroids. His Lactate level is 10mMol/L. A 55 yr old man with Group A Streptococcal Septic Shock and Necrotising Fasciitis of the thigh is sedated and fully ventilated. He is receiving much fluid, pressors and stress dose steroids. His Lactate level is 10mMol/L. Graham Hill and his group measured body composition by in-vivo electron analysis. Graham Hill and his group measured body composition by in-vivo electron analysis. 1.2G to 1.5Gm Amino Acids/Kg/day (of pre-illness body weight) seemed adequate during the first two weeks of critical illness. 1.2G to 1.5Gm Amino Acids/Kg/day (of pre-illness body weight) seemed adequate during the first two weeks of critical illness. This amount was best at reducing protein loss (not an increase in protein anabolism). This amount was best at reducing protein loss (not an increase in protein anabolism). Protein Requirements in Critical Illness. Ishibashi N et al. Crit care Med 1998;26: ) Ishibashi N et al. Crit care Med 1998;26: )

13 Nutrition: Metabolic Profiles A 55 yr old man with Group A Streptococcal Septic Shock and Necrotising Fasciitis of the thigh is sedated and fully ventilated. He is receiving much fluid, pressors and stress dose steroids. His Lactate level is 10mMol/L. A 55 yr old man with Group A Streptococcal Septic Shock and Necrotising Fasciitis of the thigh is sedated and fully ventilated. He is receiving much fluid, pressors and stress dose steroids. His Lactate level is 10mMol/L. Should you feed this man enterally or parenterally? Should you feed this man enterally or parenterally?

14 Nutritional Support in Critical Care Does enteral nutrition compared to parenteral nutrition result in better outcomes in the critically ill adult patient? Conclusions: 1) The use of EN compared to PN is not associated with a reduction in mortality in critically ill patients. 2) The use of EN compared to PN is associated with a significant reduction in the number of infectious complications in the critically ill. 3) No difference found in ventilator days or LOS between groups receiving EN or PN. 4) Insufficient data to comment on other complications; hyperglycemia or higher calories not found to result in higher mortality of infections /criticalcarenutrition.com

15 Nutritional Support in Critical Care Does enteral nutrition compared to parenteral nutrition result in better outcomes in the critically ill adult patient? /criticalcarenutrition.com

16 Nutritional Support in Critical Care Does enteral nutrition compared to parenteral nutrition result in better outcomes in the critically ill adult patient? /criticalcarenutrition.com

17 Nutrition: Metabolic Profiles A 55 yr old man with Group A Streptococcal Septic Shock and Necrotising Fasciitis of the thigh is sedated and fully ventilated. He is receiving much fluid, pressors and stress dose steroids. His Lactate level is 10mMol/L. A 55 yr old man with Group A Streptococcal Septic Shock and Necrotising Fasciitis of the thigh is sedated and fully ventilated. He is receiving much fluid, pressors and stress dose steroids. His Lactate level is 10mMol/L. Should you feed this man immediately or delay feeding? Should you feed this man immediately or delay feeding?

18 Nutritional Support in Critical Care Conclusions: 1) Early enteral nutrition, when compared to delayed nutrient intake is associated with a trend towards a reduction in mortality in critically ill patients. 2) Early enteral nutrition, when compared to delayed nutrient intake is associated with a significant reduction in infectious complications. 3) Early enteral nutrition, when compared to delayed nutrient intake has no effect on ICU or hospital length of stay. 4) Early enteral nutrition, when compared to delayed nutrient intake improves nutritional intake. Does enteral nutrition compared to parenteral nutrition result in better outcomes in the critically ill adult patient? /criticalcarenutrition.com

19 Nutritional Support in Critical Care Does early enteral nutrition compared to delayed enteral nutrition result in better outcomes in the critically ill adult patient? /criticalcarenutrition.com

20 Nutritional Support in Critical Care Does Early Enteral Nutrition compared to Delayed Enteral Nutrition result in better outcomes in the critically ill adult patient? /criticalcarenutrition.com

21 Determining Energy Expenditure indirect calorimetry: indirect calorimetry: –measurement of resting energy expenditure –measurement of O2 consumption and CO2 production –use of Weir equation: energy expenditure = (3.94 VO2) + (1.11 VCO2) energy expenditure = (3.94 VO2) + (1.11 VCO2) –sources of error: requires stable ventilation/’steady state’/stable feeding requires stable ventilation/’steady state’/stable feeding Beware high FIO 2 and system leaks Beware high FIO 2 and system leaks

22 Nutritional Support in Critical Care Recommendation: There are insufficient data to make a recommendation on the use of indirect calorimetry vs. predictive equations for determining energy needs for enteral nutrition in critically ill patients. Discussion: The committee noted the paucity of data and given the lack of treatment effect and the high costs associated with the use of indirect calorimetry (metabolic carts), despite no safety concerns, no recommendation was put forward. Indirect Calorimetry VS. Predictive Equations /criticalcarenutrition.com

23 Nutritional Support in Critical Care 3.2 Nutritional Prescription of Enteral Nutrition: Achieving target dose of enteral nutrition Recommendation: Based on 2 level 2 studies and 2 cluster randomized controlled trials, when starting enteral nutrition in critically ill patients, strategies to optimize delivery of nutrients (starting at target rate, higher threshold of gastric residual volumes, use of prokinetics and small bowel feedings) should be considered. Large improvements in calorie/protein intake/calorie deficit, decreased complications and reduced mortality with the use of enhanced enteral nutrition. Cost and feasibility concerns were also favourable. How Aggressively should we be in starting Feeding? /criticalcarenutrition.com

24 Nutritional Support in Critical Care Based on 1 level 2 study and 2 cluster randomized controlled trials, an evidence based feeding protocol that incorporates prokinetics at initiation and a higher gastric residual volume (250 mls) and the use of post pyloric feeding tubes, should be considered as a strategy to optimize delivery of enteral nutrition in critically ill adult patients. Based on 1 level 2 study and 2 cluster randomized controlled trials, an evidence based feeding protocol that incorporates prokinetics at initiation and a higher gastric residual volume (250 mls) and the use of post pyloric feeding tubes, should be considered as a strategy to optimize delivery of enteral nutrition in critically ill adult patients. /criticalcarenutrition.com Feeding protocols and Prokinetics

25 Nutritional Support in Critical Care There are inconsistent effect of Prebiotics/Probiotocs/Synbiotics on mortality. There are inconsistent effect of Prebiotics/Probiotocs/Synbiotics on mortality. There is a lack of a treatment effect on other clinical outcomes. There is a lack of a treatment effect on other clinical outcomes. Their use may be associated with a trend towards a reduction in diarrhea in the critically ill population. Their use may be associated with a trend towards a reduction in diarrhea in the critically ill population. /criticalcarenutrition.com Prebiotics/Probiotocs/Synbiotics

26 Nutritional Support in Critical Care There are insufficient data to make a recommendation on gastrostomy feeding vs. nasogastric feeding in the critically ill. There are insufficient data to make a recommendation on gastrostomy feeding vs. nasogastric feeding in the critically ill. /criticalcarenutrition.com Gastrostomy vs. Nasogastric feeding

27 Nutritional Support in Critical Care Based on 5 level 2 studies, for critically ill patients starting on enteral nutrition we recommend that parenteral nutrition not be started at the same time as enteral nutrition. In the patient who is not tolerating adequate enteral nutrition, there are insufficient data to put forward a recommendation about when parenteral nutrition should be initiated. We recommend that PN not be started in critically ill patients until all strategies to maximize EN delivery (such as small bowel feeding tubes, motility agents) have been attempted. /criticalcarenutrition.com Combination Parenteral Nutrition and Enteral Nutrition

28 Nutritional Support in Critical Care Start Early Enteral Nutrition using a small feeding tube. Start Early Enteral Nutrition using a small feeding tube. If it goes post-pylorically-great/fine. If it goes post-pylorically-great/fine. If it’s in the stomach and it works-fine. If it’s in the stomach and it works-fine. If the patient has huge gastric residuals or vomits-use prokinetics. If the patient has huge gastric residuals or vomits-use prokinetics. Just start! Just start! Gwynne Jones-very late May Parenteral Nutrition and Enteral Nutrition Advice!

29 Nutritional Support in Critical Care Have a feeding protocol. Have a feeding protocol. Any high protein to calorie ratio Enteral Nutrition formula. Any high protein to calorie ratio Enteral Nutrition formula. Escalate to maximum predicted by pre- illness weight/predictive equation. Escalate to maximum predicted by pre- illness weight/predictive equation. If the patient has huge gastric residuals or vomits-use prokinetics. If the patient has huge gastric residuals or vomits-use prokinetics. Just start! Just start! Gwynne Jones-very late May Parenteral Nutrition and Enteral Nutrition Advice!

30 Nutritional Support in Critical Care The goal of resuscitation is to maintain ATP turnover. The goal of resuscitation is to maintain ATP turnover. Fluids, Pressors and Inotropes are given to maintain “DO 2 ” Fluids, Pressors and Inotropes are given to maintain “DO 2 ” Oxygen needs fuel (Carbohydrate, Fat or Protein) to burn to maintain ATP turnover. Oxygen needs fuel (Carbohydrate, Fat or Protein) to burn to maintain ATP turnover. Glycolysis does not need Oxygen Glycolysis does not need Oxygen Gwynne Jones-very late May Resuscitation and Nutrition

31 Nutrition: Metabolic Profiles A 55 yr old man with Group A Streptococcal Septic Shock and Necrotising Fasciitis of the thigh is sedated and fully ventilated. He is receiving much fluid, pressors and stress dose steroids. His Lactate level is 10mMol/L. A 55 yr old man with Group A Streptococcal Septic Shock and Necrotising Fasciitis of the thigh is sedated and fully ventilated. He is receiving much fluid, pressors and stress dose steroids. His Lactate level is 10mMol/L.

32 Nutrition: Metabolic Profiles His metabolic Rate is His metabolic Rate is –1. At his resting level. –2. 120% of resting level. –3. 150% of resting level. –4. 200% of resting level. –5. 300% of resting level.

33 Nutrition: Metabolic Profiles StarvationCatabolic Disease Metabolic rate to Severely ill patients (septic, major trauma or post- operative) are hypermetabolic and hypercatabolic. Oxygen consumption may be increased %. This metabolic activity is needed to maintain high cardiac output and ventilatory needs, liver acute phase response and increased immunological activity for healing.

34 Nutrition: Metabolic Profiles His Body composition has changed. His Body composition has changed. –1. There is an increase of lean body mass. –2. There is an increase of Body Fat. –3. There is an increase in Total Body Water.

35 Nutrition: Metabolic Profiles Fat free body water in normal state is + 73%. Fat free body water in normal state is + 73%. This may increase to 84% in the hypermetabolic/hypercatabolic patient. This may increase to 84% in the hypermetabolic/hypercatabolic patient. This is associated with a loss of lean body mass (fewer and smaller cells). These are the working parts whose loss accounts for the progressive loss of physiological function. This is associated with a loss of lean body mass (fewer and smaller cells). These are the working parts whose loss accounts for the progressive loss of physiological function. Smaller cells reduce protein anabolic function. Smaller cells reduce protein anabolic function. Body Composition

36 Nutrition: Metabolic Profiles Weight % Body Composition Normal Critical Illness

37 Nutrition: Metabolic Profiles His Carbohydrate Metabolism has changed has changed. His Carbohydrate Metabolism has changed has changed. –1. Insulin levels are high. –2. Glucagon levels are high. –3. Catecholamines and Cortisol are high. –4. Sugar levels are high. –5. Ketone levels are low. –6. All of the above.

38 Nutrition: Metabolic Profiles Blood Sugar Blood Sugar Insulin level Insulin level Glucagon level Glucagon level StarvationCatabolic Disease or to This is the stress glucose response. There is insulin resistance both at receptor and post-receptor level. Hyperglycemia is immuno-depressive.

39 Nutrition: Metabolic Profiles Ketone production Ketone production StarvationCatabolic Disease Although ketone utilisation is still possible, the metabolism is altered such that ketones cannot be synthesised. This reduces fuel efficiency, especially in the brain, increasing energy needs and gluconeogenesis

40 Nutrition: Metabolic Profiles His Carbohydrate Metabolism has changed has changed. Sugar levels are high. His Carbohydrate Metabolism has changed has changed. Sugar levels are high. –1. Tight control of sugar levels is beneficial. –2. Tight control of sugar levels is not beneficial.

41 Nutrition: Metabolic Profiles His Fat Metabolism has changed His Fat Metabolism has changed –1. Lipolysis has increased. –2. Lipolysis has decreased. –3. Free Fatty levels are low.

42 Nutrition: Metabolic Profiles Lipolysis Lipolysis StarvationCatabolic Disease Triglygeride recycling Lipids are well used in the stress state. Lipolysis may be so activated that free fatty acid provision exceeds requirements.

43 Nutrition: Metabolic Profiles Lipolysis Lipolysis StarvationCatabolic Disease Triglygeride recycling Fatty Acids are elevated. FFAs are toxic for cell membranes and for the Mitochondria. Fatty Acids are re-esterified often producing hyperlipidemia. This is especially so with high lipid intakes. Hyperlipidemia is immuno-depressive.

44 What is our Septic Patient’s Respiratory Quotient? a) 0.7 b) 0.8. c) 0.9. d) 1.0. e) 1.2.

45 Q2 Respiratory Quotient A respiratory quotient of > 1 indicates which type of substrate utilization?: a) fat oxidation b) protein oxidation c) carbohydrate oxidation d) ethanol e) lipogenesis 10

46 Respiratory Quotient A respiratory quotient of > 1 indicates which type of substrate utilization?: RQ = VCO2 /VO2 a) fat oxidation (~ 0.7) b) protein oxidation (~ 0.8) c) carbohydrate oxidation C6H12O6 + 6O2 = 6H2O + 6 CO2C6H12O6 + 6O2 = 6H2O + 6 CO2 RQ = 1RQ = 1 d) ethanol (~ 0.67) e) lipogenesis (~ 1.2) Nutrition: Metabolic Profiles

47 Overfeeding more isn’t always better more isn’t always better CHO CHO –hyperglycemia, fatty liver –carbon dioxide production protein protein –increased urea fat fat –increased TG, hepatic steatosis, cholestasis, pancreatitis Nutrition: Metabolic Profiles

48 Q3 Refeeding Syndrome Which of the following is NOT part of refeeding syndrome? a) hypophosphatemia b) hypokalemia c) hypomagnesemia d) salt wasting e) encephalopathy Nutrition: Metabolic Profiles

49 Inflammatory bowel disease; Christie&Hill Inflammatory bowel disease; Christie&Hill Gastroenterology1990;99: Normal Value % Days of Feeding Vital capacity Why Does Strength Improve So Quickly? Grip strength

50 Refeeding Syndrome refeeding: refeeding: –sudden shift back to glucose as fuel source –hypophosphatemia –hypokalemia –hypomagnesemia Nutrition: Metabolic Profiles

51 Refeeding Syndrome management: management: –thiamine replacement –??? avoid by initiating feeds slowly (~ 25% of estimated needs on day 1) –??? gradual increase over 3 – 5 days –monitoring and replacement of electrolytes Nutrition: Metabolic Profiles

52 Nutrition: Metabolic Profiles; Protein What percentage of Protein do we Oxidise (ie Use as an energy source) in Sepsis/Stressed States. What percentage of Protein do we Oxidise (ie Use as an energy source) in Sepsis/Stressed States. –1. 5% –2. 10% –3. 15% –4. 25% –5. 40%

53 Nutrition: Metabolic Profiles; Protein What percentage of Protein do we Oxidise (ie Use as an energy source) in Sepsis/Stressed States. What percentage of Protein do we Oxidise (ie Use as an energy source) in Sepsis/Stressed States. –1. 5% –2. 10% –3. 15% –4. 25% –5. 40% The catabolism dictates that around 25% of energy needs are supplied by protein breakdown. This can be blunted by carbohydrate and fat but not totally suppressed.

54 Nutrition: Metabolic Profiles; Protein What percentage of Protein do we Oxidise (ie Use as an energy source) in Sepsis/Stressed States. What percentage of Protein do we Oxidise (ie Use as an energy source) in Sepsis/Stressed States. The catabolism dictates that around 25% of energy needs are supplied by protein breakdown. This can be blunted by food but not totally suppressed. This is the reason that normal protein intake ( ± 0.7 Gm/Kg/day) is increased to between 1.3 and 1.7 Gm/Kg/Day (Usually 1.5) in very sick patients. This is why the cans of ICU TUBE FEED have a Calorie/nitrogen ratio of 150 to 1 not the regular 100 to 1

55 Nutrition: Metabolic Profiles Minor surgery: Minor surgery: Major surgery: Major surgery: Multiple trauma/burns: Multiple trauma/burns: Head injury: Head injury: Protein Catabolism losses/day) Protein Catabolism (losses/day) 3-5g 4-10G 15-20G 20-25G G G G G N 2 /day Protein/day

56 Nutrition: Metabolic Profiles Nitrogen balance Nitrogen balance Protein turnover Protein turnover Muscle catabolism Muscle catabolism Visceral catabolism Visceral catabolism Urea production Urea production StarvationCatabolic Disease NegativeVery Negative to or

57 Nutritional Metabolic Profiles: Gut Colonisation If the Stomach has 10 2 organisms/ml. If the Stomach has 10 2 organisms/ml. How many Organisms/ml are there in the large Intestine? How many Organisms/ml are there in the large Intestine? – – – – –

58 Nutritional Metabolic Profiles: Gut Colonisation If the Stomach has 10 2 organisms/ml. If the Stomach has 10 2 organisms/ml. How many Organisms/ml are there in the large Intestine? How many Organisms/ml are there in the large Intestine? –10 10 TO How does the Stomach keep so clean? 1. Acid 2. Peristalsis 3. Both

59 Nutritional Metabolic Profiles: Gut Colonisation Stomach: 10 2 organisms/ml. Stomach: 10 2 organisms/ml. Small Intestine: intermediate numbers increasing distally. Small Intestine: intermediate numbers increasing distally. Large Bowel: organisms/ml. Large Bowel: organisms/ml. Gut Colonisation is the progressive movement of gut organisms proximally. Gut Colonisation is the progressive movement of gut organisms proximally. This process is impeded by: This process is impeded by: –Peristalsis –Stomach acidity –Normal gut ecology and food

60 Nutritional Metabolic Profiles: Gut Colonisation 1. The Gut contains 15% of the body’s immune system. 1. The Gut contains 15% of the body’s immune system. 2. Malnutrition is more dangerous than a gut that has received no food for 3 days. 2. Malnutrition is more dangerous than a gut that has received no food for 3 days. 3. TPN reduces gut translocation. 3. TPN reduces gut translocation. 4. The primary fuel source of the gut enterocytes and colonocytes is sugar. 4. The primary fuel source of the gut enterocytes and colonocytes is sugar. 5. All of the above 5. All of the above 6. None of the above 6. None of the above

61 Nutritional Metabolic Profiles: Gut Colonisation 1. The Gut contains 15% of the body’s immune system. 1. The Gut contains 15% of the body’s immune system. 2. Malnutrition is more dangerous than a gut that has received no food for 3 days. 2. Malnutrition is more dangerous than a gut that has received no food for 3 days. 3. TPN reduces gut translocation. 3. TPN reduces gut translocation. 4. The primary fuel source of the gut enterocytes and colonocytes is sugar. 4. The primary fuel source of the gut enterocytes and colonocytes is sugar. 5. All of the above 5. All of the above 6. None of the above 6. None of the above

62 NUTRITION : The gut as immune organ Fasted animals have greater metabolic response to stress than fed animals Fasted animals have greater metabolic response to stress than fed animals Human “volunteers” fed parenterally for one week have a greater metabolic response to endotoxin administration than do enterally fed “volunteers” Human “volunteers” fed parenterally for one week have a greater metabolic response to endotoxin administration than do enterally fed “volunteers” Metabolic effect lost if feeding not started within 24 hours Metabolic effect lost if feeding not started within 24 hours

63 Nutritional Metabolic Profiles : TEN VS TPN TPN and bowel rest modify metabolic response to endotoxin in humans. TPN and bowel rest modify metabolic response to endotoxin in humans. 12 healthy volunteers. Subjected to 7 days of either parenteral or enteral feed of equivalent protein & caloric content. Fasting overnight on day 7 then Am dose of endotoxin. 12 healthy volunteers. Subjected to 7 days of either parenteral or enteral feed of equivalent protein & caloric content. Fasting overnight on day 7 then Am dose of endotoxin. TPN group much sicker. TPN group much sicker. Fong et al. Ann. Surg.1989;210: Stress hormone level TNF TPN TEN

64 Aim of early enteral feeding Purported benefit of EN Direct provision of energy(glutamine, SCFA) Increased mucosal blood flow Increased biliary and pancreatic secretion Enterocyte trophic hormone stimulation Local autonomic stimulation Influence on gut permeability, translocation, metabolism Nutrition: Metabolic Profiles

65 NUTRITION : Gut hypothesis of multi-organ failure Capillary system of Gut Mucosa Gut Mucosa Arteriolar Vaso- constriction produces movement of oxygen between arteriole and venule. This leaves the villi tips ischemic. Prolonged shut-down produces necrosis of the tips of the villi. This is a precedent to translocation.

66 Nutrition: Metabolic Profiles –The propulsive peristaltic activity and its underlying myo-electrical activity need sustained activity to maintain their function. –Absence of food –Electrolytes/Opiods/Shock Factors Aggravating Paralytic Ileus: Factors Aggravating Paralytic Ileus:

67 Nutrition: Metabolic Profiles Elective abdominal surgery depresses muscle protein synthesis and increases fatigue B Peterson et al. Br.J.Surg1990; 77: Fatigue Post-operative day

68 Immune Enhancing Feeds. 10 good studies: 9 showed benefit 10 good studies: 9 showed benefit Bower et al.(Crit.Care.Med.1995;23: ) randomised 326 ICU pts. to standard or enhanced enteral formulae. Decreased infection rate and length of stay with enhanced formula (Impact) Bower et al.(Crit.Care.Med.1995;23: ) randomised 326 ICU pts. to standard or enhanced enteral formulae. Decreased infection rate and length of stay with enhanced formula (Impact) Nutrition: Metabolic Profiles

69 Immune Enhancing Feeds.

70 Glutamine Conditionally essential Conditionally essential Most abundant amino acid Most abundant amino acid Fuel for dividing cells Fuel for dividing cells –enterocytes, lymphocytes, macrophages Released from muscle with stress, sepsis Released from muscle with stress, sepsis Low plasma and intracellular concentration with stress (correlates with mortality) Low plasma and intracellular concentration with stress (correlates with mortality) Nutrition: Metabolic Profiles

71 NUTRITION : Human outcome of immune enhancing enteral feeding protocols. Glutamine It is an essential precursor of nucleotide synthesis It is an essential precursor of nucleotide synthesis It serves as a primary substrate for renal ammoniagenesis and arginine synthesis It serves as a primary substrate for renal ammoniagenesis and arginine synthesis Glutamine + Cysteine + Glycine = Glutathione. Combined with Selenium, this is a major intra-cellular anti-oxidant. Glutamine + Cysteine + Glycine = Glutathione. Combined with Selenium, this is a major intra-cellular anti-oxidant.

72 NUTRITION :Glutamine Circulating glutamine pool GUT MUSCLE KIDNEY LIVER LYMPHOCYTE MACROPHAGE PMN FOOD LUNGS ACID/BASE NH4 Glutamate Gln. in Gln.

73 Glutamine Nutrition: Metabolic Profiles

74 NUTRITION : Human outcome of immune enhancing enteral feeding protocols. The role of Glutamine. Glutamine supplementation demonstrated a significant reduction in mortality (Risk Ratio,0.76, 95% confidence interval ). Glutamine supplementation demonstrated a significant reduction in mortality (Risk Ratio,0.76, 95% confidence interval ). Glutamine supplementation demonstrated a significant reduction in length of stay (Weighted mean difference in days -4.50, 95% CI to ). Glutamine supplementation demonstrated a significant reduction in length of stay (Weighted mean difference in days -4.50, 95% CI to ). The position of the Canadian Critical Care Trials Group. Based on meta-analysis of randomised controlled trials.

75 Nutrition: Metabolic Profiles ‘conditionally essential’ amino acid ‘conditionally essential’ amino acid –endogenous synthesis limited with illness –also arginase upregulated in critical illness precursor for proline, glutamate, NH3 detoxification precursor for proline, glutamate, NH3 detoxification role in nitric oxide synthesis role in nitric oxide synthesis L-arginine NO + citrulline Arginine

76 Nutrition: Metabolic Profiles arginine supplementation rationale: arginine supplementation rationale: –sepsis associated with low serum arginine levels –low levels may correlate with worse outcome –needed for normal T-cell function –increased NO may improve microcirculatory flow and immune function however: however: –no good evidence of benefit –possibility of harm in septic patients Arginine

77 Nutrition: Metabolic Profiles recommended as supplement in PN (trace element) recommended as supplement in PN (trace element) patients with shock have low Se levels patients with shock have low Se levels Se is cofactor in glutathione function and also immune effect Se is cofactor in glutathione function and also immune effect additional supplementation may improve outcome additional supplementation may improve outcome Selenium

78 NUTRITION : Human outcome of immune enhancing enteral feeding protocols. Selenium and Anti-oxidants. Selenium supplementation (>500ug) demonstrated a significant reduction in mortality (Risk Ratio,0.52, 95% confidence interval ). Selenium supplementation (>500ug) demonstrated a significant reduction in mortality (Risk Ratio,0.52, 95% confidence interval ). Zinc + Vits. A,C, E supplementation demonstrated a mild reduction in mortality of 0.65 (95% CI ). Zinc + Vits. A,C, E supplementation demonstrated a mild reduction in mortality of 0.65 (95% CI ). The position of the Canadian Critical Care Trials Group. Based on meta-analysis of randomised controlled trials.

79 NUTRITION : Human outcome of immune enhancing enteral feeding protocols. Fatty Acids essential FA: EN supplemented with essential FA: EN supplemented with –EPA (fish oil) –GLA (borage oil) –antioxidant vitamins: E, C Changes cell membrane flexibility and signalling. modulation of leukotriene and cyclooxygenase pathways Changes cell membrane flexibility and signalling. modulation of leukotriene and cyclooxygenase pathways omega-3 (alpha linoleic acid) omega-3 (alpha linoleic acid) – precursor for eisonanoids 1.omega-6 (linoleic acid) – precursor for arachidonic acid – potentially proinflammatory (TNF, interleukin) – vasoconstriction, platelet aggregation

80 NUTRITION : Human outcome of immune enhancing enteral feeding protocols. Fish Oils – Fish Oils Enriched EN improved survival in patients with ARDS/ALI – ? decrease ventilator days and organ failure

81 Nutrition: Metabolic Profiles Take Home Messages Take Home Messages –Food is Part of a – Normal Diet

82

83 Nutrition: Metabolic Profiles Take Home Messages Take Home Messages An Empty Gut is a Dangerous Gut

84 Nutrition: Metabolic Profiles Take Home Messages Take Home Messages An Empty Gut is a Dangerous Gut. You are the Parasite-there are more bugs in your gut than human cells

85 Nutrition: Metabolic Profiles Take Home Messages Take Home Messages An Empty Gut is a Dangerous Gut. Pre-operative fasting is getting shorter and shorter. See NHS website

86 Nutrition: Metabolic Profiles Take Home Messages Take Home Messages An Empty Gut is a Dangerous Gut. Post-operative fasting is getting shorter and shorter. Start on POD1 See NHS website

87 Nutrition: Metabolic Profiles Take Home Messages Take Home Messages An Empty Gut is a Dangerous Gut. Post-operative fasting is getting shorter and shorter. Give Food not clear fluids. Warren et al. Nutrn in Clin Practice 2011;26:

88 Nutrition: Metabolic Profiles Take Home Messages Take Home Messages An Empty Gut is a Dangerous Gut. Posture and Deportment See NHS website

89 Nutrition: Metabolic Profiles Take Home Messages Take Home Messages An Empty Gut is a Dangerous Gut. Posture and Deportment. Eating Sitting is Easier. 45° necessary in the Ill. See NHS website

90 Nutrition: Metabolic Profiles Take Home Messages Take Home Messages For Critical Care Nutritional information see: criticalcarenutrition.com

91 CARBON DIOXIDE A Second Class Molecule


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