Surgical Foundations – Sep 7, 2011 Dr. Alfonse Marchie Dr. Natasha Cohen Dr. Shezad Tejani Dr. Tiffaney Kittmer Guest Expert: Michele ApSimon, MSc, RD Outline     Metabolism Nutritional Requirements Adaptation to Stress Nutritional Support "One man’s food is another man’s poison."  Roman healer and philosopher Lucretius- 55 BC Metabolism  Metabolism is the body's biochemical anabolic (creating or synthesizing) and catabolic (breaking down) reactions  Rate at which one burns calories  Basal metabolic rate (BMR)- rate your body burns calories in a rested state  Average adult’s BMR about 1,200 to 1,800 calories per day Factors that affect Metabolic Rates          Weight Exercise Gender, race, age Hormones Pregnancy Stress Temperature Food Other Calculating the BMR  Male= 66.5 + (13.8 x BW in Kg) + (5 x height in cm) (6.8 x age)  Female= 65.5 + (9.6 x BW in Kg) + (1.7 x height in cm) (4.7 x age)  100 patients admitted to surgical ward  Malnutrition Universal Screening Tool (MUST)  33% had high scores-high malnutrition risk  Longer hospital stay (19 days vs. 5 days)  Mortality higher Populations at Risk for Malnutrition        Neonates Cancer receiving chemotherapy Major trauma, burn injuries Inflammatory bowel disease Chronic renal failure Chronic neurological disorders Fever, sepsis Clinical Sequelae of Impaired Nutrition      Hypoproteinemia Inability to handle excess salt/water intake Bowel edema inhibits GI function Wound edema inhibits healing Prevents normal cardiovascular response to shock Clinical Sequelae of Impaired Nutrition  Muscle wasting  Impairs ventilating capacity and susceptibility to ventilatory failure and chest infection  Impaired cell mediated immunity  Susceptibility to infection Nutritional assessment     Clinical (history and physical examination) Anthropometry Biochemical tests Body composition History  Anorexia, nausea, and vomiting  Chronic or recent weight loss  Unintentional weight loss = ↑ complications Preoperative unintended weight loss and low body mass index in relation to complications and length of stay after cardiac surgery  Lenny MW van Venrooij, Rien de Vos, Mieke MMJ Borgmeijer-Hoelen, Cees Haaring, and Bas AJM de Mol  Preoperative unintended weight loss (UWL) in cardiac surgery patients  Examined 330 patients  Preoperative UWL of ≥10% in the past 6 mo associated with a prolonged length of stay  Preoperative BMI ≤ 21.0 was associated with increased incidence of postoperative infections & prolonged stay in the intensive care unit Definitions <10% - mild malnutrition, over 1 month 10-20%- moderate malnutrition, over 1 month >20% - severe, in 6 months >30% - pre-morbid >50% - pre-mortality Physical Exam  Weight and height  Hair loss, skin breakdown, peripheral edema, and muscle wasting  Muscle strength Anthropometry  Frontal-occipital head circumference (FOC)  Triceps skin-fold (TSF) thickness  Mid-arm circumference (MAC) Biochemical Tests     Albumin (T1/2 = 21days) Prealbumin Retinol-binding protein Delayed Cutaneous Hypersensitivity (DH) Prognostic Nutritional Index  PNI%= 158- 16.6(albumin) – 0.78(TSF) – 0.2(TFN) – 5.8(DH)  TSF= Triceps skin fold thickness in mm  TFN= Transferrin  DH = Delayed hypersensitivity (may be substituted with lymphocyte score) Prognostic Inflammatory Nutrition Index (PINI)  PINI = (CRP)(AAG) (PA)(ALB) where CRP= C-reactive protein, AAG= alpha 1-acidglycoprotein, PA= pre-albumin, ALB=albumin Energy  Energy is required continuously for normal  organ function  maintenance of metabolic homeostasis  heat production  performance of mechanical work Estimated Energy Requirements EER: •Dietary energy intake that is predicted to maintain energy balance in a healthy individual. – In children, it includes the needs associated with growth. For most healthy infants and children, the equations here can be used to determine energy needs. – ~1 kcal/kg/hour •a. For infants, children, and adolescents, EER (kcal/day) = TEE + energy deposition (required for growth) •b. For most hospitalized patients, it can be assumed PAL = sedentary, PA = 1 Health Canada • Adults – EER(kcal/day) = Total Energy Expenditure – Men • – EER = 662 - (9.53 x age [y]) + PA x { (15.91 x weight [kg]) + (539.6 x height [m]) } Women • EER = 354 - (6.91 x age [y]) + PA x { (9.36 x weight [kg]) + (726 x height [m]) } » PA = physical activity coefficient Resting energy expenditure • Def: Amount of energy (calories) required for 24h for a non-active period • Liver, intestine, brain, kidneys, and heart – 10% of total body weight – account for approximately 75% of REE. • Skeletal muscle at rest – 40% of body weight – approximately 20% of REE • Adipose tissue – more than 20% of body weight – consumes less than 5% of REE Indirect calorimetry  Resting energy expenditure (REE), respiratory quotient (RQ) and substrate utilization will be calculated from measurements of oxygen (VO2) and carbon dioxide (VCO2) in inspired and expired air  Respiratory quotient:  RQ = VCO2 / VO2 Respiratory quotient  An RQ may rise above 1.0 for an organism burning carbohydrate to produce or "lay down" fat (for example, a bear preparing for hibernation)  RQ value corresponds to a caloric value for each liter (L) of CO2 produced TEE  Total daily energy expenditure (TEE)  resting energy expenditure (~70% of TEE)  expenditure of physical activity (~20% of TEE)  thermic effect of feeding (~10% of TEE),  temporary increase in energy expenditure that accompanies enteral ingestion or parenteral administration of nutrients Metabolic stress • TEE = REE X stress factor • In acutely ill hospitalized patients, it is usually not necessary to include an activity factor Energy in Metabolic Stress  An alternative and rather simple formula for adult inpatients  20-25 kcal/kg of actual body weight (ABW)/day for unstressed or mild stress  25-30 kcal/ABW/day for moderate stress  30-35 kcal/ABW/day for severe stress  ABW can be misleading (lean body mass) if >30% of ideal body weight (IBW)  Adjusted IBW = IBW+ 0.33(ABW− IBW) Protein  20 amino acids are found commonly in human proteins  Essential amino acids cannot be synthesized by the body  histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, valine, and possibly arginine  Non-essential amino acids – can be made endogenously  glycine, alanine, serine, cysteine, cystine, tyrosine, glutamine, glutamic acid, asparagine, and aspartic acid  The U.S. Recommended Daily Allowance (RDA) of protein is 0.8 g/kg/day Protein in Health • The body of an average 75-kg man contains approximately 12 kg of protein. • In contrast to fat and carbohydrate, there is no storage for protein • excess intake is catabolized and the nitrogen component is excreted • As metabolic stress/rate increases, nitrogen excretion increases proportionately • 2 mg nitrogen (N)/kcal of REE Protein in illness • Nonessential amino acids may become essential – Termed: conditionally essential amino acids – wound healing appear to be improved in critically ill patients by the inclusion of supplemental glutamine in total parenteral nutrition (TPN) because of cellular depletion of this amino acid. – parenteral glutamine has benefits in patients with particularly high severity of illness scores (e.g., high APACHE II or SOFA scores) – Similarly, it cysteine and tyrosine are essential in with cirrhosis because of impaired hepatic synthesis Albumin Normal man has 280g. Turnover is 9-12g daily. Half life is 15-28 days. Pre-Albumin half life is 2 days - correlates better with nutritional status.  Albumin falls in stress because liver switches to producing acute phase proteins such as CRP and ferritin.     Nitrogen Balance  Proxy for protein balance  N balance = grams of N administered as nutrition – (urinary urea N[g] + 4)  6.26g of protein = 1g of Nitrogen Carbohydrate  Principal dietary digestible:  Starch, sucrose and lactose  no absolute dietary requirement for carbohydrate  glucose can be synthesized from endogenous amino acids as well as glycerol  5 to 20 g of indigestible carbohydrate (soluble and insoluble fibers) are consumed daily.  Carbohydrate intake stimulates insulin secretion    inhibits muscle protein breakdown stimulates muscle protein synthesis decreases endogenous glucose production from amino acids  glucose is the required fuel for:      red and white blood cells renal medulla eye tissues peripheral nerves Brain  glucose requirements for these tissues are met ( 150 g/day) Lipids • Triglycerides (TGs), sterols, and phospholipids • Serve as: – sources of energy – precursors for steroid hormone, prostaglandin, thromboxane, and leukotriene synthesis – structural components of cell membranes – carriers of essential nutrients • Dietary lipids are composed mainly of TGs, which contain saturated and unsaturated long-chain fatty acids (FAs) of 16 to 18 carbons. Lipids • The use of fat as a fuel requires the hydrolysis of endogenous or exogenous TGs and cellular uptake of released Fatty Acids • Long-chain FAs are transferred across mitochondrial membranes by a carnitine dependent transport system. • Once inside the mitochondria, FAs are degraded by beta oxidation to acetyl coenzyme A (CoA), which then enters the TCA cycle. • A decrease in the number of mitochondria or oxidative enzymes associated with aging or deconditioning favors the use of carbohydrate as fuel. Essential fatty acids  Humans lack the desaturase enzyme  needed to produce the n-3 (double bond between carbons 3 and 4) and n-6 (double bond between carbons 6 and 7) FA series.  Linoleic acid (C18 : 2, n-6) and linolenic acid (C18 : 3, n3), therefore, should constitute at least 2% and 0.5%, respectively, of the daily caloric intake to prevent essential FA deficiency (EFAD). EFAD & Risk factors  Essential FA stores in adipose tissue  Thought to be protective for essential fatty acid deficiency  However…  abnormal FA profile in conjunction with a clinical syndrome of EFAD is now known to occur sometimes in adults with severe short bowel syndrome who are on long-term total parenteral nutrition (TPN) that lacks parenteral lipids Major Minerals  Definition:  Inorganic nutrients that are required in large quantities (>100mg/d)  important for ionic equilibrium, water balance, and normal cell function.  Malnutrition and nutritional repletion can have dramatic effects on major mineral balance. Electrolytes Micronutrients • Vitamins and trace minerals • Used as coenzymes, prosthetic groups, biochemical, substrates or hormones Vitamins  Fat soluble  ADEK  Do not serve as co-enzymes  Absorption through micelles  Water soluble  Co-enzymes Trace elements  Evidence exists that there are 10 essential nutrients in humans:  Iron, Zinc, Copper, Chromium, Selenium, Iodine, Fluorine, Manganese, Molyndenum and Cobalt  Iron most commonly deficient, then zinc  Chronic GI issues (s.a. IBD) known to precipitate zinc deficiency Vitamin A Vitamin D, E Vitamin K Trace Minerals Trace Minerals Introduction  Impaired Nutrition  Nosocomial infections  Longer Hospital stay  Impaired Wound Healing  Loss of Muscle Function and Wasting  Ventilatory Performance and Dependence  Rationale for Effective use of Nutritional therapy  Dynamics of metabolic response to challenge:  Starvation Vs. Surgical Stress Adaptations to Food Deprivation Short-Term Fasting  Insulin and Glucagon  Hepatic Glycogenolysis (100g) for glucose mainteinance  Fat  Bulk of calories, releasing free fatty acids and glycerol  Protein Mobilization  Amino Acids  Normal Turnover: 2.5% to 3%  300g of protein / day Initially  Decreased Protein synthesis and Increased Degradation Short-Term Fasting  Peripheral Tissues: FFA and Ketone Bodies Utilization for ATP and Inhibition of Glucose Utilization  BCAA Oxidation in Muscle  Glycogen reserves exhausted within 48 hrs.  Gluconeogenesis in the Liver and Kidney via Glutamine, Alanine, Lactate and Glycerol  Maintenance of Blood Glucose for Brain, Erythrocytes and Kidney Long-Term Fasting  Initially: 75g of muscle protein = 300g of muscle per day mobilized for gluconeogenesis  If continues  1/3rd of total body protein exhausted in 3 wks  Long Term Starvation: Major Metabolic Adaptation  CNS switches fuels to ketone bodies  Shift from Protein source to Fats (Ketones)  Protein Sparing and Preserving Functional Role.  Obligatory Proteolysis  20 g protein /d  1 Wk of Starvation  Diminished AV difference in AA and by decreased urinary N-methylhistidine excretion Endocrine / Metabolic Response to Surgery  The “Stress” Response  Neuroendocrine: Sympathetic Nervous System  Endocrine : HPA System  Inflammatory: Cytokines  Substrate Mobilization  Energy  Salt and Volume Retention Response To Surgery Two Phases Ebb Phase  Transitory over 24 hrs  Depression of body`s physiological functions  Blood Flow, Temp and Oxygen Utilization Rise of Stress hormones Accumulation of Water, proteins and Na at site of injury Flow Phase  Hypermetabolic State  Catabolic Phase Increased Loss of Nitrogen and other body constituents Sympathetic Response  Catecholamines / NE – Presynaptic nerve terminals and Adrenal Medulla  Tachycardia and HTN  Renin - Ang I  Ang II  Aldosterone Na reabsorption  Glucagon - Glycogen breakdown and FFA mobilization Endocrine  Pituitary  ACTH and GH  Vasopressin  Cortisol  above 1500 nmol / L within 4-6hrs of major surgery. Levels related to severity of insult.  Skeletal muscle protein breakdown  Lipolysis  Mineralocorticoid Effects Endocrine  Growth Hormone  Glycogenolysis and Lipolysis  Glucose uptake and utilization inhibited  Role in reducing protein catabolism  Insulin  Release inhibited through inhibition of B-cells by alphaadrenergic inhibitory effects of catecholamines.  Insulin Resistance state  Thyroid  T4 and T3 -- Oxygen consumption and increased metabolic rate and heat production Substrate Mobilization Carbohydrate Metabolism  Hyperglycemia – Catecholamines and Cortisol  Regulation of glucose via Insulin ineffective due to initial insulin inhibition and resistance.  High glucose state – impair wound healing and infections Lipid Metabolism  High Catecholamines, Cortisol and Glucagon and low Insulin promote lipolysis and ketone production.  FFA – Acyl CoA – Ketone in liver Substrate Mobilization Protein  Net Protein Catabolism        Inhibition of protein anabolism Enhanced Catabolism via Cortisol and Cytokines Increased Amino Acid turnover – negative Nitrogen balance. Proteolysis increase over 45% (600 to 800g of muscle loss per day) Protein Degradation co-relates with type of surgery and Nutritional status Skeletal muscle followed by Visceral muscle Functional Compromise Metabolic Response To Trauma Severity of Trauma: Effects on Nitrogen Losses and Metabolic Rate Protein Catabolism: Starvation Vs. Surgery  Muscle, Free AA and all body proteins involved in catabolic state including Serum proteins  Albumin, Prealbumin and Transferrin  Serum protein concentrations fall more rapidly in and to greater extent with starvation following surgery than with starvation alone  Surgical Stress – accelerates breakdown of proteins and increases turnover in setting of limited substrates. Starvation Vs. Surgery Starvation vs. Surgery  Both present a nutritional and metabolic challenge  Similar processes initiated  In Starvation: Metabolic Adaptation resulting in reduction of energy expenditure of up to 40% and limitation of proteolysis from 75g to 20g per day  Post-op / Trauma: These mechanisms limiting proteolysis are either impaired or non-operative = net Nitrogen loss Nutritional Support     Indications Types Benefits Complications Indications for Nutritional Support Poor nutritional status (oral intake <50% of energy needs) Catabolic disease (burns, sepsis, pancreatitis) Significant weight loss (>10%) Anticipated need for more than 7 days of nutritional support  Non-functioning gastrointestinal tract  Albumin <30 g/L in the absence of an inflammatory state     Types  Enteral  Oral  Naso-gastric/duodenal/jejunal  Orogastric  Gastric/gastrojejunal  Jejunal  Parenteral  Central line  Peripheral intravenous Enteral Feeds  “If the gut works, use it!”  Avoids complications of venous catheters  Mimics normal flow of nutrients from GI tract to liver, likely beneficial to hepatic function  May improve immune function  Mechanism suspected to be related to IgA production  May promote maintenance of GI mucosa’s integrity  has been shown in burns and hemorrhagic shock Enteral Feeds  Cheap, easy, effective  With large-calibre tubes can check residuals  Generally check q4h  Goal: residuals <150ml  Many of the tubes traverse the GE junction  GERD, aspiration are resultant problems, no matter where the end of those tubes are sitting  Absolute contraindications  Bowel ischemia, perforation, peritonitis, mechanical obstruction Parenteral Feeds  Peripheral  Only safe for short-term (4-7 days)  Glucose concentration limited to max 5%  Better than nothing, but usually can’t meet a sick patient’s full nutritional requirements via this route  Central  I.e. Tip of catheter in the SVC  Can be used for longer term TPN  Higher concentrations Choose the route!  78 F with dysphagia from an ischemic stroke with good rehab potential vs with poor rehab potential  55 M with generalized peritonitis from perforated cecal volvulus presenting one day later in severe septic shock, stay complicated by leak on POD2 from his right hemicolectomy  24 M with mild pancreatitis vs in ICU with severe pancreatitis  74 F multi-trauma, intubated in ICU and awaiting definitive repair of her R femur # in about 1 week TPN Content  2-in-1: amino acids and dextrose  3-in-1: amino acids, dextrose and lipids (much more common)  Common additions: TPN Math  Goal: 25-35 kcal/kg/day  Lipids: 20% of caloric intake (omit if doing a 2 in 1 mix)  Protein: 1.5 g/kg/day  Carbohydrates: the remainder to reach caloric intake  Reference values  Glucose: 3.4 kcal/g  Protein: 4 kcal/g  Lipids: 9 kcal/g TPN Calculation Case  67 year-old 80kg male with severe radiation enteritis.  1) Total caloric requirement (25-35 kcal/kg/day)  2) Daily protein requirement (1.5g/kg/day)  3) Lipid component (20% of calories)  4) Use dextrose for the rest of needed calories  5) Check maximums    Max Carb: 5g/kg/day Max Protein: 2g/kg/day Max Lipids: 2.5g/kg/day Caloric Content Glucose: 3.4 kcal/g Protein: 4 kcal/g Lipids: 9 kcal/g TPN Calculation Answers  1) Total caloric requirement (25-35 kcal/kg/day)  30kcal/kg/day X 80kg = 2400 kcal/day  2) Daily protein requirement (1.5g/kg/day)  1.5g/kg/day X 80kg = 120g/day  120g X 4kcal/g = 480 kcal  3) Lipid component (20% of calories)  2400 X 0.2 = 480 kcal  480 kcal / 9 kcal/g = 53.3 g  4) Use dextrose for the rest of needed calories  Total – protein – fat = 2400 – 480 – 480 = 1440 kcal  1440 kcal / 3.4 kcal/g = 424 g  Put it all together: 120g of protein, 53g of lipids, 424g of dextrose  5) Check maximums  Max Carb: 5g/kg/day = 400g (24g over)  Max Protein: 2g/kg/day = 160g (ok)  Max Lipids: 2.5g/kg/day = 200g (well under) TPN Monitoring  Clinical  Weights, signs of infection  Bloodwork  CBS q6h  Baseline and daily until stable: lytes, ext lytes, BUN, Cr, glucose  Baseline and weekly: LFTs, albumin, TGs, INR TPN Risks  Catheter  Line infection     More lumens = higher infection risk (triple vs single lumen) PICC = higher incidence of leakage, malpositioning, thrombophlebitis compared to central lines, same rates of sepsis Hyperglycemia increases incidence of infection 80% of infections are Staph aureus/epidermidis TPN Risks Line thrombosis  Line placement complications          Pneumothorax Thoracic duct injury Arterial/venous injuries Air embolus Catheter embolus Chronic pain Brachial plexus injury Erosion of catheter into nearby structures TPN Risks Cont’d  Liver dysfunction: cholestasis, steatosis, cirrhosis  Full mechanism still being elucidated       Hypertriglyceridemia Overfeeding ?inflammation-mediated hepatocellular damage ?deficiencies ?lack of hormone activation ?glucagon/insulin imbalance resulting in lipogenesis  Decreased bone mineral density “Immunonutrition”  Feeds enriched in nutrients (such as arginine, omega-3 fatty acids & nucleotides) to modulate host immunity  Literature to support this not strong  Daly et al 1992 – post-op immunonutrition vs standard nutrition  Problem: control group formula isocaloric, but less protein  Braga et al 1995 – pre- and post-op immunonutrition vs standard fare  Problem: results not replicated in subsequent studies  Both above studies and meta-analyses show trends toward reduced infection rates and decreased length of stay in tx groups, but cannot fully attribute this to the additives due to study design issues and data heterogeneity  The debate continues Questions? Resources  www.criticalcarenutrition.com  Sabiston Textbook of Surgery – Chapter 7  Cecil Medicine – Chapters 220-225  Michele ApSimon [email protected]