N U TRITION A N D C R I TICALLY I L L PATIENTS W I TH S E P S I S

Transcription

1 N U TRITION A N D M E TABOLISM: C R I TICALLY I L L PATIENTS W I TH S E P S I S A R T H U R R. H. V A N Z A N T E N, M D P H D I N T E R N IST - IN TENSIV IST H O S P I T AL M E D I C A L D I R E C T OR G E L D E R S E V A L L E I H O S P I TAL, E D E, T H E N E T H E R L A N D S E - M A I L : Z A N T E N A@ZGV.N L 1

2 Overview Metabolism in Sepsis Full or Trophic Feeding Enteral feeding and vasopressors Proteins in Sepsis Micronutrients in Sepsis Immune-modulation in Sepsis

3 Metabolism in Sepsis

4 Nitrogen loss N loss in g/day Burns Trauma Severe Sepsis Infection Elective Surger Partial starvatio Full starvation Normal days

5 Resting Energy Metabolism REE in % Burns Peritonitis Fracture Partial starvation Full Starvation Normal days

6 Resting Energy Metabolism If you cannot estimate is measure it. Indirect Calorimetry

7 Full or Trophic Feeding?

8 Enteral nutrition guidelines: Critically ill patients ASPEN 2016 N4. Based on expert consensus, we suggest the provision of trophic feeding (defined as kcal/h or up to 500 kcal/d) for the initial phase of sepsis, advancing as tolerated after hours to >80% of target energy goal over the first week. We suggest delivery of g protein/kg/d.

9 Effect of daily increase of 1000 kcal or 30 g proteins & 60 d mortality risk BMI group Energy Adj. Odds Ratio kcal/day 95%CI LCL 95% CI UCL P- value Effect if BMI <25 or >35 overall < to < to < to < to < N=2729/272 8 Proteins + 30 g proteins/day overall < to < to < to < to < C Alberda Intensive Care Med. 2009;35(10):

10 Young patients, high BMI, severely ill ICU patients Arabi et al. New Engl J Med May online first

11 Caloric and Protein Intake Arabi et al. New Engl J Med May online first

12 Trophic vs. Full EN in ICU patients: ARABI RCT No effect of hypocaloric feeding in young, overweight patients when protein intake is compensated! Average age 50 Average BMI All fed within 24 hrs (benefits of early EN) Pseudomulticentric almost 70% of the patients from one site. No indirect calorimetry Mean caloric intake 11 kcal vs. 16 kcal per kilogram of body weight per day Both intakes met the criteria for underfeeding. Mean protein intake achieved (0.7 g per kilogram per day in both groups) was far below the recommended intake of 1.2 to 2.0 g per kilogram per day. Trophic Full EN Elke G, Van Zanten AR. New Engl J Med, May 20, 2015 Arabi et al. New Engl J Med May online first

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14 12-day Caloric Adequacy & 60-Day Hospital Mortality Optimum 80-85% Percent of caloric prescription received in first 12 days Heyland D et al. Crit Care Med 2011

15 Hospital mortality and cumulative energy deficit during first 4 days of ICU stay for 726 non-septic ICU patients P = Optimum 80-90% Reference is the measured resting energy expenditure of the patient Weijs P. Crit Care 2014;18:701

16 Effect of energy and protein intake in sepsis Elke et al. Critical Care 2014, 18:R29

17 Is EN safe during periods of hemodynamic instability in adult critically ill patients?

18 Contraindications for Early Enteral Nutrition? Proven Bowel ischemia High fistula that cannot be bypassed Refractory shock Bowel obstruction In our ICU > 96% of patients do not have contraindications for early enteral nutrition in the first 24 hours after ICU admission

19 Always resuscitate patient before starting EEN Fluid therapy Vasopressor start Stable MAP (>65 mmhg) Acceptable ScVO2 (65-70%) Acceptable lactate < 2.5 mmol/l or 50% drop Most patients are stable within 6-12 hours Then start EEN (<24h) In our ICU we did not encounter 1 single case of non-occlusive mesenteric ischemia due to EN in more than 1000 ICU patients using this checklist

20 Percent survival Safe on vasopressors? 100 Retrospective analysis prospectively collected data more than two days on vasopressor agents Early feeding <48 h Late feeding >48 h 707 patients patients Days post-intubation Both in 1 and > 1 vasopressors significant better survival in early feeding Khalid I. Am J Crit Care. 2010;19:

21 Enteral nutrition guidelines: Critically ill patients ASPEN 2016 N1. Based on expert consensus, we suggest that critically ill patients receive EN therapy within hours of making the diagnosis of severe sepsis/septic shock as soon as resuscitation is complete and the patient is hemodynamically stable.

22 Protein dose in Sepsis?

23 Protein Balance in Sepsis Catabolism Protein-degradation in sepsis 2,2 g protein.kg -1.day -1 (1,4 for starving healthy persons) Anabolism Maximum protein synthesis 1,5-1,7 g Protein.kg -1.day -1 cbwt Feeding the critically ill is different

24 Protein Dose in Sepsis Early protein intake 1.2 g/kg at day 4 is associated with lower and early energy overfeeding with higher hospital mortality in non-septic mechanically ventilated critically ill patients. In sepsis patients no relation was found between early protein intake and mortality. Weijs P et al. Crit Care 2014, 18:701

25 Micronutrients in Sepsis?

26 Antioxidants and Oxidative Stress Koekkoek, Van Zanten, Submitted

27 Antioxidants and oxygen radicals Koekkoek, Van Zanten, Submitted

28 Micronutrients & mortality (not exclusively sepsis) < 10% mortality > 23% mortality

29 Enteral nutrition guidelines: Critically ill patients ASPEN 2016 N3. We cannot make a recommendation regarding selenium, zinc, and antioxidant supplementation in sepsis at this time due to conflicting studies. No data of MetaPlus, REDOXs trial Only studies up to 31 December 2013

30 Antioxydants/vitamins/trace elements/selenium Consider to use Antioxydants/vitamins/trace elements/selenium in all ICU patients RDA is available in 1500 ml of EN Many patients do not reach this targets for days

31 Immune-modulation in Sepsis?

32 Enteral nutrition guidelines: Critically ill patients ESPEN and ASPEN ESPEN (2006) Enteral should be started with a high-protein formulae No general indication for immune-modulating formulas in patients with severe illness or sepsis and an APACHE-II-score >15 SCCM / ASPEN (2009) Recommended protein intake is g/kg bw per day Immune modulating enteral formulae (supplemented with agents such as arginine, glutamine, nucleic acid, omega-3 fatty acids and anti-oxidants) should be used for the appropriate patient population including critically ill patients on mechanical ventilation

33 Persistent inflammatory, immunosuppressed, catabolic syndrome (PICS): A new phenotype of multiple organ failure Theory 1 Theory 2 Rosenthal MD, et al. J Adv Nutr Hum Metab 2015; 2: e784. doi: /janhm.784 Hotchkiss R. Nature Reviews Immunology 13, (2013)

34 Fish oil in Prostate Cancer Dots and horizontal lines correspond to relative risks (RRs) and 95% confidence intervals (CIs), respectively, comparing the highest vs lowest quantile of EPA Decreased risk with higher blood levels of DPA (clupanodonic acid, commonly called DPA is an intermediary between eicosapentaenoic acid (EPA, 20:5 ω-3) and docosahexaenoic acid (DHA, 22:6 ω-3). But an increased risk of more aggressive prostate cancer with higher blood levels of combined EPA and DHA, and some evidence of an association between high blood levels of omega-3 fatty acids and an increased prostate cancer risk Brasky ThM, JNCI J Natl Cancer Inst djt174 doi: /jnci/djt174

35 Immunonutrition and sepsis Lack of knowledge Arginine enteral associated with increased mortality risk, possibly due to production of citrulline and NO Many studies on glutamine, concept challenged Fish oil debated

36 MetaPlus Study Netherlands A.R.H van Zanten, Ziekenhuis Gelderse Vallei, Ede, CI M.L.H. Honing, Medisch Centrum Alkmaar Germany A.Sablotzki, Klinikum St Georg, Leipzig U.X. Kaisers, Universitätsklinikum Leipzig S. Zielmann, Heinrich-Braun-Klinikum, Zwickau T. W. Felbinger, Klinikum Neuperlach, Munich O.Keh, Charité Universitätsmedizin, Berlin France J-F Zazzo, Hôpital Antoine Béclère, Clamart J-F Timsit, Hôpital Universitaire Albert Michallon, Grenoble F. Sztark, Hôpital Pellegrin - CHU de Bordeaux Belgium J. de Waele, UZ Gent, Gent J-L Vincent J-C Preiser, Erasme University Hospital, Brussels Van Zanten AR et al. JAMA 2014 Aug 6;312(5):

37 Product compositions during ICU stay up to maximum of day 28 Nutrients (per 1500 ml) IMHP HP Energy 1920 kcal 1920 kcal Protein (g) Cas/ wheat hydr / Ala-Gln Glutamine Carbohydrates Fructose g (23.4 En%) 41% / 39% / 20% 30 g 141 g - (29.3 En%) 0 g g (23.4 En%) 100 %/0/0 9 g 231 g - (48 En%) 0 g Fat MCT EPA DHA Anti-oxidants vitamin C vitamin E (alpha toco) Selenium Zinc 96 g (45 En%) 19.5 g 7.5 g Above normal values 690 mg 266 mg (400 IU) 285 mcg 30 mg 55.5 g (26.3 En%) 0 g 0 g Normal values 195 mg 22.5 mg mcg 22.5 mg Other Vit / Min./ trace el. Normal values Normal values Fiber 22.5 g (2.3 En%) 22.5 g (2.3 En%) Van Zanten AR et al. JAMA 2014 Aug 6;312(5):

38 Incidence new infections Primary Outcome Measure IMHP HP P value All n=152 n=149 53% 52% Medical (IMHP n=54 vs. Protison n=55) 39% 47% Surgical (IMHP n=81 vs. Protison n=75) 62% 51% Trauma (IMHP n=55 vs. Protison n=54) 58% 67% % of subjects with at least one infection after start study product, using CDC-infection criteria No statistical significant differences between IMHP and Protison based on Chi square tests. Van Zanten AR et al. JAMA 2014 Aug 6;312(5):

39 Mortality 28-days mortality Incidence (%) 6-months mortality Incidence (%) IMHP HP p value IMHP HP p value All (n=168) 20% 17% All (n=297) 35% 28% Medical (n=109) 35% 24% Medical (n=109) 54% 35% Surgical (n=156) 14% 16% Surgical (n=152) 27% 28% Trauma (n=109) 7% 4% Trauma (n=107) 15% 17% Differences between IMHP and HP based on Chi square tests. Van Zanten AR et al. JAMA 2014 Aug 6;312(5):

40 6-months mortality Cox hazard model After predefined covariates were tested in univariate analysis Hazard Ratio Lower Limit Upper Limit P value IMHP vs. Protison Age (70-80 vs. age (>80) Age (50-70) vs. age (>80) <0.001 Age (<50) vs. age (>80) <0.001 APACHE-II score (unit) <0.001 After adjustment for age and APACHE-II score, risk of death is 57% higher for patients on IMHP versus control feed patients (P=0.036) pre-defined covariates: age ( 50, 51-70, 71-80, >80 yrs), sex, BMI, APACHE-II score, adj. pred. mortality, screening SOFA score, baseline glutamine, baseline glucose, type of patient (medical, surgical non trauma, surgical trauma, trauma non surgical), start study product since ICU admission, occurrence of pre-existing infection, and treatment with antibiotics at start of study. The final model was constructed using univariate screening followed by a stepwise variable-selection procedure. Van Zanten AR et al. JAMA 2014 Aug 6;312(5):

41 Conclusions Abnormal metabolism in sepsis High nutritional risk, expected long stay Estimation of REE difficult, indirect calorimetry recommended Full feeding sepsis probably better than trophic feeding Start EEN after resuscitation, then it seems to be safe High protein is recommended in non-septic patients Optimum protein intake in sepsis unclear ( g/kg per day) Pharmacological dosages of micronutrients not indicated (yet) EN intake <1500 kcal/day consider vitamin and trace element supplementation Immune-modulating macronutrients probably not safe.

42 THANK YOU