Metabolic and Nutritional Support of the Trauma Patient Bradley J. Phillips, MD Burn-Trauma-ICU Adults & Pediatrics

Historical Prospective (Metabolic and Nutritional Support) “Starve a fever, feed a cold” 300 BC ,100 AD - Aristotle, Galen -” vital heat “ 1600’s Harvey, Van Helmont - heat related to circulation, heat is lost due to death 1920’s Cuthbertson - hypermetabolic response to injury

Metabolic response to injury The metabolic responses to critical illness /trauma evolve over time Metabolic needs reflexed the phase of the injury response Phases of the injury response : ebb,flow, convalescence

Ebb phase: 24 - 48 hrs fluid retention elevated counter Regulator hormones glycogenolysis, Lipolysis

EBB phase Decrease cardiac output Decrease oxygen consumption Decrease temperature Increase blood sugar, lactate levels, normal to low Insulin levels

Flow phase: - Post ebb ,variable time course Hypermetabolic muscle catabolism Hyperglycemia Elevated Free fatty acids

Flow phase Increase cardiac output Increase body temperature Increase 02 consumption Increase blood sugar, Insulin

Convalescence / Recovery Phase: weeks to months anabolic decrease in total body edema, return of GI function weight gain

Metabolic Response to Injury Substrate mobilization: mixed fuel of glucose,protein and Lipid. Glucose via glycogen then hepatic and renal gluconeogenesis. (lactate, glycerol, alanine). Protein from peripheral stores to provide alanine and substrates for hepatic acute phase proteins. Lipid mobilized from peripheral stores via lipolysis to generate free fatty acids and glycerol.

Neuroendocrine Response to Injury Counter Regulatory hormones Glucagon Epinephrine Norepinephrine Growth hormone Cortisol

Cytokine Cascade TNF  IL-1 and IL-6. Releases from multiple cell types after injury or infection. TNF  IL-1 and IL-6. IL-1 > TNF, IL-6 stimulate pituitary - adrenal axis. Glucocorticoids inhibit cytokine release, reduces cytokine MRNA.

Neuroendocrine/Cytokine Response to Injury Stimuli Hemorrhage, ECF loss Hypoxemia Pain/anxiety Change in temperature Change in substrate availability Tissue injury

Injury/Stress : Carbohydrate metabolism glycogenolysis gluconeogenesis increase liver production and peripheral uptake insulin residence hyperglycemia

Carbohydrate Metabolism in stress HORMONES: counter - regulatory Glucagon, epinephrine, norepinephrine cortisol - counter act hypoglycemia Epinephrine -  glycogenolysis,  gluconeogenesis  glucagon Glucagon -  liver production of glucose, dose not effect clearance Insulin -  production from B cells, resistance Postreceptor Cortisol potentiates other hormones effects glucose,AA and Fatty acid metabolism

Carbohydrate Metabolism in Stress Cytokines: TNF -  hepatic glucose productions,  glucose uptake in peripheral tissue IL - 1 -  plasma glucose -  hepatic production  peripheral glucose transport

Injury/stress : Protein metabolism Protein catabolism Protein synthesis is up, but the net rate of brake down is greater. AA mobilized from skeletal muscle to fuel wound healing , the cellular inflammatory response and acute phase protein production, AA oxidized for fuel Protein catabolism poorly suppressed by exogenous fuels

Protein Metabolism in stress Hormones - muscle counter regulatory hormones increase muscle protein brake down Cortisol,glucagon and catecholamines -  muscle breakdown GH/IGF-1 -  levels in stress anabolic Insulin - inhibits protein break down

Protein metabolism in Stress Hormones - liver epinephrine -  APP,  AA transport glucagon -  APP,  AA transport cortisol -  AA, enhance other hormone,cytokine effects GH -  AA transport

Protein Metabolism in Stress CYTOKINES: TNF, IL-I - increase protein breakdown in muscle, may inhabit effects of IGF - 1 IL-6 -  APP production as do IL-I, TNF,IFN Cytokines and hormones interact to effect protein synthesis in the liver and protein breakdown in muscle

Injury/Stress : Lipid metabolism Increases fat metabolism ,increased serum FFA,Triglycerides  clearance of triglycerides,  lipoprotein lipase activity  Lipolysis  Synthesis of liver Apolipoproteins and triglycerides - denovo + recycled FFA

Lipid Metabolism in stress HORMONES: Effect of counter regulator hormones on lipid metabolism unclear Epinephrine  Lipolysis in adipose tissue Glucagon -  FA synthesis in the liver Cortisol -  FA synthesis in adipose tissue does not effect liver FA synthesis Insulin -  FA synthesis in hepatocyte

Lipid Metabolism in Stress Cytokines: TNF -  serum triglycerides -  hepatic FFA and triglyceride synthesis,  Lipolysis in adipose tissue  serum FFA; glycerol IL-1, IFN-’s -  Lipolysis,  Lipoprotein Lipase :effect many aspects of hepatic Fatty acid synthesis

Metabolic Response to Injury Substrate mobilization: mixed fuel of glucose,protein and Lipid. Glucose via glycogen then hepatic and renal gluconeogenesis. (lactate, glycerol, alanine). Protein from peripheral stores to provide alanine and substrates for hepatic acute phase proteins. Lipid mobilized from peripheral stores via lipolysis to generate free fatty acids and glycerol.

Metabolic Response to Injury Ebb phase - fuel mobilization Flow phase - catabolic Convalescence - anabolic Counter Regulatory hormones Cytokines TNF,IL-1 and IL-6.

Nutritional Assessment

Nutritional Assessment Who to feed ? When and How to feed ? What to feed ?

Nutritional Assessment Who to feed ? Only those patients who will benefit Only those patients whose risks of complications from malnutrition are greater then the risks of nutritional interventions

Nutritional Assessment Who to feed ? Malnourished patients > 10% Wgt. Lose. NPO > 5-7 days. Patient expected to be NPO > 7-10 days.

Nutritional Support How: Use the gut. It’s natural. Protects the patient from the TPN Doctor.

Nutrient Composition What to feed ? How much energy ?

Hypermetabolism of Injury Major surgery 10% > baseline. Trauma 25% > baseline. Large burn injury 100% > baseline.

Energy Requirements of Injury Measured need : indirect calorimetry E.E. = (3.94 x VO2 ) + (1.1 x VCO2 ) Estimated energy needs: Harris-Benedict men: EE= 66+(13.8xwgt) + (5xHt) -(6.8xage) women: EE= 665+ (9.6xwgt) + (1.7xHt) - (4.7xAge) 25kcal/Kg/day.

Indirect calorimetry Metabolic cart

Metabolic cart in critical illness Indirect Calorimetry Metabolic cart in critical illness Resting energy expenditure of critically ill patients varies widely over the course of the day and over the course of an illness Measurements from - 10 % to + 23 % of an “average” REE can be seen within a 24 hour period

Predicting REE Harris-Benedict is correct 80-90% of the time Indirect Calorimetry Predicting REE Harris-Benedict is correct 80-90% of the time in healthy, normal volunteers. In 10-14% it over estimates EE In obese normal volunteers it predicts EE correctly in only 40-64% in critically ill patients the Harris-Benedict equation is correct only 50% of the time For most disease processes Harris -Benedict underestimates EE

Predicting REE Multipliers for various disease states attempt Indirect Calorimetry Predicting REE Multipliers for various disease states attempt to improve the accuracy of the Harris-Benedict equation These multipliers tend to overestimate EE when compared to indirect calorimetry

Nutrient Composition - Energy Complications of under feeding ? Morbidity and mortality of malnutrition Complications of over feeding? Hyperglycemia, fatty liver , respiratory failure, immunosuppression,etc . 25kcal/Kg/day will avoid over or under feeding of most critically ill patients.

Nutrient Composition What ? Protein. Carbohydrate. Fat.

Substrate Provision Protein: metabolic stress leads to; proteolysis of skeletal muscle,increased Hepatic synthesis of APP,increased use of AA for energy production. Net nitrogen lose 1.5 gram/kg/day. > 1.4 gram/kg/day leads to both an increase in protein synthesis and catabolism with no net gain for the patient. Glutamine, Arginine.

Substrate Provision Carbohydrates: Glucose primary fuel for the injury response. Injury/stress effect ability to oxidize glucose Stable post-op patient maximum glucose oxidation rate 7mg/kg/min. Stressed patient maximum glucose oxidation rate 5mg/kg/min.

Substrate Provision Carbohydrates: maximum glucose oxidation rate: 5mg/kg/min. Avoid: over feeding, hyperglycemia (BS < 220 mg/dL).

PREVALENCE OF HYYPRGLECEMIA IN TPN PATIENTS 260 TPN patients screened, 102 low risk patients evaluated . 22 % ( 23/102) of low risk patients had BS > 200mg/dl Glucose infusion:mg/Kg/min < 4 4.1 - 5 > 5 Patients BS > 200 mg/dl 0 (0 %) 5 (11 %) 18 (50 %) Patients BS < 200 mg/dl 18 41 19 Rosemarin DK, et al, Nutri. Clin Pract, 1996;11:151-6

Substrate Provision Carbohydrates: maximum glucose oxidation rate: 5mg/kg/min.

Substrate Provision- lipid Lipid: Fat metabolism is increased in stress, increased lipolysis, increased fatty acid oxidation, increased production and release from the liver . Lipid administration prevents essential fatty acid deficiency ,spares protein. Lipid administration has cardiopulmonary and immunologic effects

Substrate Provision Lipids: Provide EFA’s. Provide calories that avoid hyperglycemia. Mixed fuel may enhance protein sparing. Cardiovascular effects. Immunologic effects. giving lipid in low concentrations and slowly <0.1 gr/kg/hr of iv lipid

Substrate Provision Lipids: Cardiopulmonary effects. Alterations in diffusion,shunting and oxygenation Immunologic effects. Overload REE system,impair neutrophil chemotaxis, modulate eicosanoid production Effects can be modulated by : choice of lipid; giving lipid in low concentrations and slowly; <0.11gr/kg/hr of iv lipid

Effects of IV Lipid in Trauma Patients: Lipid (n=30) No Lipid (n=27) P Age 33 ± 10 32 ± 9 _ ISS 27 ± 8 30 ± 9 _ Apache II 25 ± 6 22 ± 5 _ On Ventilator* 27 ± 21 15 ± 12 0.01 ICU Los* 29 ± 22 18 ± 12 0.02 Hospital Los* 39 ± 24 27 ± 16 0.03 Survival 30/30 25/27 Non-protein kcal/kg 29 ± 2 22 ± 1 % kcal as Lipid 25 ± 4 0 Amino Acids (g/kg-d) 1.6 ± 0.2 1.5 ± 0.1 * in days, LOS = length of stay Data expressed means ± SD Battistella et al. J Trauma 39: 164, 1995

Conclusion N.S. essential to Rx/avoid malnutrition and its complication. N.S. only helpful for patients at risk and if given correctly. Avoid over feeding. Avoid hyperglycemia. Lipid at low concentrations, given slowly.

Nutritional Support Energy - 25 kcal/kg/day Glucose - Do not exceed 5mg/kg/min Protein - 1.5 gr/kg/day Lipid - Do not exceed 0.11 gr/kg/hr

Conclusion Metabolic response to injury evolve over time . Responses are under hormonal and cytokine control Hypermetabolism after injury is variable. Nitrogen loss, muscle wasting and hyperglycemia. Outcome from injury can be enhanced by the judicious use of nutritional support.

Questions…?