Disclosures. None. Enteral Nutrition and Vasoactive Therapy! But actually.. Stocks Advisory boards Grants Speakers Bureau. Paul Marik, MD,FCCM,FCCP

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1 Enteral Nutrition and Vasoactive Therapy! Paul Marik, MD,FCCM,FCCP Disclosures Stocks Advisory boards Grants Speakers Bureau None But actually.. 1

2 We suggest a determination of nutrition risk (NUTRIC score) be performed on all patients admitted to the ICU We suggest that indirect calorimetry (IC) be used to determine energy requirements [Quality Evidence; Very Low] In the absence of IC, we suggest a weight-based equation (25 3 kcal/kg/day) Enteral feeding should be started early within the first hours following admission Patients who are at high nutrition risk (NUTRIC score 5) efforts to provide 8-1% of goal calories within hours Protein requirements of g/kg/day BW [Quality Evidence; Very Low] We suggest using a standard polymeric formula when initiating EN in the ICU setting. We recommend that enteral feeding protocols be designed and implemented to increase the overall percentage of goal calories provided. [Quality of Evidence: Moderate to High] We suggest that use of a volume-based feeding protocol or a top-down multistrategy protocol be considered We suggest that for high-risk patients or those shown to be intolerant to bolus gastric EN, delivery of EN should be switched to continuous infusion. In the patient determined to be at high nutrition risk (NUTR IC score 6) when EN is not feasible, we suggest initiating exclusive PN as soon as possible following ICU admission 2

3 Why Feed the Critically ill? Limit loss of lean body mass (skeletal muscle) Immune modulation Prevent infections Maintain /Enhance immune function Attenuate pro-inflammatory response Promote tissue repair and wound healing Maintain integrity of the GI tract NEJM 23; 348:683 NEJM 23; 348:683 NEJM 211; 364:1293 Crit Care 28; 12:R79 Puthucheary ZA et al. JAMA 213;31:1591 3

4 Role of disease and macronutrient dose in the randomized controlled EPaNIC trial Predictors of muscle wasting MSOF vs single organ failure Age ICU Length of stay Amount of enteral protein delivered Puthucheary ZA et al. JAMA 213;31:1591 Casaer MP, et al. Am J Respi Crit Care Med 213; 187:247 Role of disease and macronutrient dose in the randomized controlled EPaNIC trial Does achieving nutritional goals within 48 hours of ICU admission improve patient outcomes? Protein dose Glucose dose Casaer MP, et al. Am J Respi Crit Care Med 213; 187:247 Mortality 4

5 Infections Does achieving nutritional goals within 48 hours of ICU admission improve patient outcomes? Short term Anorexia is an evolutionary preserved response during acute illness starvation beneficial may be Mediated largely by pro-inflammatory cytokines and PG-E 2 Leptin and orexin Starvation promotes autophagy 5

6 Intermittent Feeding Continuous Feeding No species eats continuously (day and night) and such an evolutionary design would seem absurd. The alimentary tract and metabolic pathways of humans appear designed for intermittent ingestion of nutrients a few times a day. Intermittent bolus feeding has a greater stimulatory effect of protein synthesis in skeletal muscle than continuous feeding in neonatal pigs Bohe J et al. J Physiol 21;532.2:775 Gazzaneo M, et al. J Nutr 211;141;2152 Intermittent bolus feeding has a greater stimulatory effect of protein synthesis in skeletal muscle than continuous feeding in neonatal pigs 35 Protein Synthetic rate (%/day) GLP-1 GIP 1 IEN CEN PN IEN CEN PN 5 Starvation Continuous Bolus Gazzaneo M, et al. J Nutr 211;141;2152 6

7 No evidence that underfeeding is harmful Bolus feeding is more effective in stimulating muscle synthesis than continuous feeding Evidence suggests that more protein may be harmful (continuous) Ann Surg 215 Pressors and Enteral Feeding! Paul E. Marik, MD, FCCP; Vikramjit Khangoora, MD Michael Hooper, MD, Msc; John D Catravas, PhD, FAHA, FCCP Racquel Rivera, Pharm D Mechanistic Pathways in Sepsis Vitamin C is a cofactor for the synthesis of norepinephrine Vitamin C is a cofactor for the synthesis of vasopressin Vitamin C is a cofactor for the synthesis of dopamine Vitamin C is a cofactor for the synthesis of cortisol Vitamin C is a cofactor for the synthesis of collagen Vitamin C binds α-adrenergic receptors increasing activation Vitamin C binds β-adrenergic receptors increasing activation Time to pressor discontinuation Norepinephrine eq ug/min Hours Treatment Control-Alive Control-Dead 7

8 Time to pressor discontinuation Treatment Group Norepineprine eq ug/min Pressor Dosage Over Time α-agonists (vasopressors) and vasopressin Redistribute blood towards the brain and vital organs Redistribute blood away from: Splanchnic bed Skin Extremities Vasopressin impairs microcirculatory flow increasing the risk of ischemia Hours Mean time to discontinuation of all pressors 18.3 ± 9.8 Hyperemic Response to Enteral Nutrients Luminal nutrients are trophic to the GI tract and important for maintenance of structure and function (including the gut barrier and immune system) These effects are mediated by direct and indirect effects (ie. hormonal) Enteral nutrients augment gut blood flow, primarily via locally mediated vasodilation Hyperemic Response Nutrient augmentation of blood flow aids oxygen delivery to the gut and absorption of nutrients following a meal Flow is increased in all layers of the gut (mucosa, submucosa, muscularis) In contrast, gut blood flow is diminished during fasting This effect of nutrients on blood flow is known as the Postprandial Hyperemic Response Hyperemic Response Studies have evaluated dietary components for their ability to increase mesenteric flow (via dilatation) Increased blood flow primarily results from the dietary content of peptides, simple carbohydrates, & long chain fatty acids Complex nutrient solutions increase blood flow greater than individual constituents FAT > CHO meals GUT Blood Flow Gut blood flow is diminished during various forms of critical illness (ie. sepsis, hemorrhage, multitrauma, burn, cardiogenic shock) Gut blood flow remains below normal despite volume resuscitation (suggests presence of intrinsic vasoconstrictors) Decreased blood flow is associated with microbe translocation, ischemic bowel, multiorgan failure Increasing gut blood flow would appear to be beneficial 8

9 Vasopressor Gut Blood Flow Evaluated EN in 9 pts requiring hemodynamic support with catecholamines 1 day after cardiac surgery During EN cardiac index increased (14%) and indocyanine green clearance increased 31% (splanchnic blood flow) Zaloga et al. Nutr Clin Prac 23;18:285 Early Enteral Nutrition Can Be Safely Used in Hemodynamically Unstable Patients Objective Evaluate whether early EN can be used safely in hemodynamically unstable patients Subjects All subjects had >2 days of vasopressors and mechanical ventilation Design Data prospectively collected, retrospectively analyzed Treatment groups Early EN (n = 77): received EN within 48 hours of MV initiation Late EN (n = 467): did not receive early EN Outcomes Primary: overall ICU and hospital mortality Khalid I, et al. Am J Crit Care. 21;19:261 Early Enteral Nutrition Can Be Safely Used in Hemodynamically Unstable Patients Patients, % p <.1 Early EN 28.3 ICU Mortality Late EN 33.8 p < Hospital Mortality The beneficial effect of early EN was more evident in patients treated with multiple vasopressors (odds ratio.36; 95% CI,.15.85). Khalid I, et al. Am J Crit Care. 21;19:261 Enteral Feeding-Associated Bowel Necrosis Rare; <1% in most series Most reported in 8 s and 9 s Major abdominal surgery or trauma Large volume feeding directly into jejunum Hypotension and use of vasopressors rarely reported before bowel necrosis; most patients hemodynamically stable Most cases in patients receiving delayed EN (D5-1) Enteral Feeding-Associated Bowel Necrosis **Underlying bowel injury **Decreased perfusion secondary to bowel dilation Clonidine (α2 agonist) decreased motility redistribution of blood flow Almost all with jejunal feeding 9

10 ABCD of Resuscitation Airway Breathing Circulation Vitamin C + Corticosteroids Diet Gastric may be easier and safer Bolus rather than continuous HOLD feeds for marked abdominal distention & acute hypotension Initiate feeding After hrs Choose the right Formula Whey Protein, MCT, O-3 FA, 1.2 cal/ml VITAL 1.2 Feed correctly BOLUS FEED 1ml q4 hr over 2 mins 15ml q4 hr over 2 mins Optimize Feeding Advance slowly 2ml q4 hr over 3 mins 25ml q4 hr over 4 mins 3ml q4 hr over 45 mins 1