Nutrition and Sepsis - PDF Free Download

Nutrition and Sepsis Todd W. Rice, MD, MSc Associate Professor of Medicine Vanderbilt University 2017 DNS Symposium June 2, 2017

Case 55 y.o. male COPD, DM, HTN, presents with pneumonia and septic shock. He has acute renal failure with creatinine 1.8. Intubated in ED, started on norepinephrine drip, and admitted to MICU. On 70% FiO2, PEEP 12.

Objectives 1. Review evidence on Nutrition Support of Critically Ill Patients with Sepsis a) Understand when to feed critically ill patients with severe sepsis / shock and respiratory failure b) Discuss data on amount of EN to provide critically ill patients with severe sepsis c) Comprehend data concerning composition of EN formulas for patients with severe sepsis 2. Outline urgent areas for further research of nutrition in patients with sepsis

Nutrition Questions How should we feed him? Enteral vs. Parenteral; Gastric vs. Post-pyloric When should we start feeding him? Right away vs. few days vs. out of shock How much should we feed him (goals)? Trophic vs full-calorie What should we feed him? TF du jour vs. special formula;? Anti-oxidants What safety measures should we employ? Gastric residual volume level; GI intolerances

When should we start EN in patients with severe sepsis or septic shock?

Timing of Enteral Nutrition 1. Consensus guidelines recommend starting enteral nutrition and increasing to target rates within a few days in patients who are going to be without nutrition for at least 3 days 2. However, observational data suggests early EN (< 48hrs) is associated with improved outcomes 3. Recent meta-analyses suggest starting EN within 24 hours improves survival 1,2 Small (6 studies, 234 pts) Trauma, Burn pts very few med or med/surg 1. Doig, et al. Intensive Care Med. 2009;35:2018-2027. 2. Doig GS, et al. Injury. 2010; 42:50-56.

Doig, et al. Intensive Care Med. 2009;35:2018-2027 OR 0.34 (0.14, 0.85) OR 0.31 (0.12, 0.78)

How much should we feed patients? (especially early in sepsis)

Quantity of Enteral Feeds Limited data suggest initiating EN w/in 24 hrs is beneficial (esp trauma) But those data don t address quantity of enteral feeding If we start enteral feeds within 24-48 hours, do we have to get to target or goal rates as soon as possible?

Effects of EN McClave SA, et al. CCM. 2014;42(12):2600-2610.

Trophic Feeds The minimum amount of enteral nutrition required for the mucosal benefits is unknown As little as 10-40% of caloric requirements preserves mucosal structure in dogs 1 and pigs 2 Trophic= nourishment or growth Low volume continuous feeds for the purpose of nourishing the intestinal mucosa 1. Owens L, et al. J of Nutrition. 2002;132:2717-22. 2. Burrin DG, et al. Am J Clin Nutr. 2000;71:16

Conflicting Guidelines SSC 2012 Avoid mandatory full feeding; suggest low dose (up to 500 kcal/d) in first week (2B) Canadian Crit Care Nutrition 2013 Optimize dose of EN and not use initial strategy of trophic feeds for 5 days ASPEN / CCM 2016 Trophic feeding (10-20kcal/hr) initially, advancing as tolerated over 24-48 hours to > 80% of target energy over first week. 1. Dellinger RP, et al. CCM. 2013;41(2):580-637. 2. Dhaliwal R, et al. Nutr Clin Pract. 2014;29:29-43. 3. Taylor BE et al. CCM. 2016;44(2):390-438.

13630 pts from 3 international nutrition studies MV w/in 48 hrs of ICU admission and ICU LOS 3d 2270 (from 351 ICUs) had sepsis or pneumonia 61.7 y.o.; BMI 27.6; APACHE II 23.9 EN started 26.6hrs; 1,057 kcal / d (61% goal); 49 g / d protein (0.7g/kg/d) 60d Mortality: 30.5%; MV 8.4 d; ICU LOS 11.5 d Elke G, et al. Crit Care. 2014;18:R29.

OR 0.61 (0.48, 0.77) OR 0.76 (0.65, 0.87) Elke G, et al. Crit Care. 2014;18:R29.

Elke G, et al. Crit Care. 2014;18:R29.

894 critically ill patients 7 hospitals in Saudia Arabia and Canada 75% medical, 21% non-op trauma 96% MV, 55% on pressors Randomized, open label trial 40-60% goal cal + protein vs 70-100% goal kcal for up to 14 days Primary Endpoint: 90 day mortality Arabi YM, et al. NEJM. 2015;372(25):2398-2408.

Arabi YM, et al. NEJM. 2015;372(25):2398-2408.

Arabi YM, et al. NEJM. May 20, 2015; Epub Ahead of Print.

Arabi YM, et al. NEJM. 2015;372(25):2398-2408.

1000 mech vent patients with ALI Mostly Medical Pneumonia (65%); Sepsis (15%) 38% on vasopressors at enrollment EN started about 24 hours from intubation Factorial design with n-3 fatty acid / placebo Trophic (N=508) vs. Goal (N=492) for first 6d Primary endpoint: Ventilator-free days

EDEN: Enteral Feeds Delivered * * * * * * * * * * * * *P<0.001

Percent of On Study Days EDEN: Percent of Feeding Days with Specific GI Intolerances 20 16 12 Trophic (N=508) Full (N=492) 8 4 P=0.05 P<0.001 P=0.003 P=0.003 0 efig 1: NHLBI ARDS Network. JAMA. 2012; 307(8):795.

EDEN: Outcomes P=0.89 P=0.67 P=0.77 NHLBI ARDS Network. JAMA. 2012; 307(8):795.

EDEN: Baseline (Sepsis & PNA) Characteristic Trophic n=424 Full n=373 P-Value Age 52.9 ± 16.6 52.9 ± 15.0 0.95 Female (%) 49 52 0.33 Caucasian (%) 76 77 0.53 APACHE III 93.0 ± 27.8 92.4 ± 26.9 0.77 On Vasopressors (%) 37% 39% 0.59 Diabetes (%) 26% 27% 0.78 Creatinine (mg / dl) * 1.6 ± 1.5 1.8 ± 1.6 0.09 Glucose (mg / dl) 134 ± 56 137 ± 48 0.40 Albumin (g / dl) 2.3 ± 0.6 2.3 ± 0.6 0.52

EDEN (Sepsis & Pneumonia): Main Outcomes Outcome Trophic (N=424) Full-Cal (N=373) P-value Mortality (%) 60-day 90-day 24.5% 25.5% 22.5% 23.1% 0.51 0.43 VFD to day 28 (days) 14.6 ± 11.0 14.7 ± 10.5 0.88 ICU free days to day 28 14.1 ± 10.3 14.6 ± 9.8 0.50 ARDS Network. Unpublished Data

Should we use any special formulas or supplements in feeding patients with sepsis?

N-3 Fatty Acids in Sepsis (Pre-ALI) Pontes Arruda et al, Crit Care 2011 Blinded RCT of 106 adults with sepsis in ICU < 36hrs No organ failures, getting tube feeds start w/in 12 hrs; goal 75% of Harris Benedict x 1.3 N-3 (Oxepa ) vs. Carbs (Ensure HN ) x 7 days Endpoint: Development of organ failure / shock Avg Age 71 y.o.; 70% Pneumonia; 60% malnourished Baseline APACHE II 20; SOFA 6 -??????? Pontes-Arruda A, et al. Crit Care 2011;15:R144.

N-3 Fatty Acids in Sepsis (Pre-ALI) Organ Failures (26.3 vs. 50%) Shock (21 vs 36%) ICU-free days Mech Vent Hospital-free days Improved Clinical Outcomes No diff in mortality (26 vs. 28%) Pontes-Arruda A, et al. Crit Care 2011;15:R144.

N-3 Fatty Acids in ARDS Three initial studies suggested improved outcomes with n-3 FA in ARDS 1-3 But compared to high N-6 FA formula Not all patients included / analyzed More recent, larger studies failed to demonstrate benefit 4-6 One (OMEGA) demonstrated potential harm 4 Two used supplementation / bolus 4,5 Two included anti-oxidants 4,6, 1 glutamine 6? IV n-3 fatty acids 1. Gadek JE, et al. CCM. 1999;27:1409-1420. 2. Singer P, et al. CCM. 2006;34:1033-1038. 3. Pontes-Arruda A, et al. CCM 2006;34:2325-33. 4. Rice TW, ARDSnet, et al. JAMA. 2011;306:1574-1581. 5. Stapleton RD, et al. CCM. 2011;39(7):1655-1662. 6. VanZanten AR, et al. JAMA. 2014;312:514-524.

Glutamine and Anti-Oxidants Numerous studies mostly without benefit Recent studies have resulted in safety questions One (OMEGA) combined AO with omega-3 FA 1 One (MetaPlus) combined AO, glutamine, n-3 FA 2 One (REDOX) factorial glutamine and selenium 3 All 3 with some signal of harm REDOX with higher mortality in patients with multisystem organ failure / renal failure 4 1. Rice TW, ARDSnet, et al. JAMA. 2011;306:1574-1581. 2. VanZanten AR, et al. JAMA. 2014;312:514-524. 3. Heyland DK, et al. NEJM. 2013;368:1489-1497. 4. Heyland DK, et al. JPEN. 2015;39(4):401-409.

Arginine in Sepsis Theoretical concern over increased NO production and hypotension Recent studies have given arginine to patients with sepsis without worsening shock 1,2 Arginine improved tissue perfusion, increased cardiac output, decreased protein catabolism 1 Older multicenter RCT found reduced nosocomial infections with arginine containing immunonutrition enteral formula 3 1. Liuking YC, et al. Clin Sci. 2015;128(1):57-67. 2. Visser M, et al. Br J Nutr. 2012;107(10):1458-1465. 3. Galban C et al. CCM. 2000;28(3):643-648.

Citrulline in Sepsis Citrulline is precursor to arginine production Citrulline negative feedback on NOS Unpublished RCT of IV citrulline did not cause or worsen hypotension No difference in oxidative stress, S/F, Nox No significant difference in clinical outcomes but trend toward dose dependent reduction in hospital mortality Placebo 22.7%; Low Dose 19.2%; High Dose 12.5% Rice TW, et al. AJRCCM. 2017;A7438.

Nutrition Questions How should we feed him? Enteral; Gastric When should we start feeding him? Right away (assuming some hemodynamic stability) How much should we feed him (goals)? Trophic vs permissive underfeeding vs. full-calorie What should we feed him? TF du jour, +/- protein supplementation No omega-3 FA, Anti-oxidants, glutamine Arginine may be okay

Research Topics for Nutrition in Sepsis RCTs of optimal amount of calories specifically in patients with sepsis Amount of protein to feed? Should we supplement? Immunonutrition Omega 3 FA s; Arginine or Citrulline Carbohydrate / Protein / Fat composition of EN Optimal timing of initiating EN in septic shock patients

THANK YOU!!!! Questions?