Ernährungstherapie des Kritisch Kranken Enteral Parenteral Ganz egal?

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1 Ernährungstherapie des Kritisch Kranken Enteral Parenteral Ganz egal? PD Dr. med. Claudia Heidegger Service des Soins Intensifs Genf/Schweiz Dresden 11. Juni 2016

2 Nutrition News Nutrition controversy in critically ill patients about optimal timing amount of macronutrients route of feeding Accepted! Early EN (24-48h ) = standard of care for hemodynamically stable ICU patients with functioning GI-tract Conflicting results of recent RCTs of EN vs. PN Discordant opinions & different interpretations Contradictory or complementary? Best clinical practice???

3 Appropriate nutrition support for the individual ICU patient Medical condition Nutritional status Available routes ACCP Consensus statement, 1997

4 Malnutrition & poor outcome in critically ill patients Malnutrition 20-40% Incidence of complications Infections & MOF Time on MV Mortality ICU & hospital LOS Costs Picture by M. Donnier/Soins Intensifs-HUG, 2013 Giner et al.; Nutrition 1996; 12:23-9 Kyle et al., Clin Nutr 2006; 25: Middleton et al., Intern Med J 2001;31: Martin et al., Can Med Ass J 2004; 170:

5 Energy support in critically ill patient considering age & disease phase Energy delivery kcal/kg Young patient Old patient acute (day 0-3) old young stabilized (>day3) old young Acute Phase (72-96h): endogenous substrates utilisation Ł Risk of overfeeding! Bodyweight (actual) Ockenga J. et al., Akt Ernährungsmed 2012; 37: 22-27

6 Usually feeding practices in the ICU Prospective observational cohort study EN 69%; PN 8%; EN + PN 18%; no EN or PN 5% BMI<20 BMI 40 BMI ICUs from 37 countries (5 continents) 2772 mechanically ventilated adult patients ICU stay for 72 hours Data collection: 12 days Average intake» 1000 kcal/day 1000kcal/d 60-day mortality; p=0.02 days on MV; p=0.01 c/o BMI < 25 or 35!!! Alberda et al., Intensive Care Med, 2009;35:

7 What is the optimal nutrition support for the critically ill? ENTERAL (EN) or PARENTERAL (PN)???

8 ESPEN GUIDELINES 2006/2009 Energy intake & disease stage Gold standard: Indirect Calorimetry Acute Phase (72-96h): kcal/kg/d Post Acute Phase: kcal/kg/d Severe Undernutrition: kcal/kg/d Severe sepsis, trauma,burns: 40 kcal/kg/d «All patients who are not expected to be on a full oral diet within 3 days should receive EN» «All patients receiving less than their targeted enteral feeding after 2 days should be considered for supplementary PN» Kreyman et al., Clin Nutr 2006; 25: Singer et al., Clin Nutr 2009;28:

9 ENTERAL or PARENTERAL? Enteral Nutrition: Superior to Parenteral Nutrition? More physiological: Use the gut if you can Maintenance of intestinal trophicity Preservation of immune and gut barrier function Preservation of intestinal microbial diversity Infectious risk No risk of hepatic dysfunction Better regulation of insulin secretion and glycemia Lower risk of overfeeding and Refeeding syndrom Lower costs

10 Unintentional hypocaloric feeding is current in the critically ill patient!!! Caloric intake < 70% A prospective survey of nutritional support practices in ICU patients: Medical ICU over a 9 months period delivered prescribed required De Jonghe B et al., Crit Care Med 2001; 29:8 12

11 But TPN? TPN = Total Poisonous Nutrition

12 TPN negative points? Association with gut mucosal atrophy Metabolic complications Hyperglycaemia Hypertriglyceridaemia Infectious complications Liver dysfunction Danger of overfeeding

13 Evidences from Clinical Studies

14 Effects of early EN (48h) on the outcome of critically ill mechanically ventilated medical patients Retrospective analysis of a prospectively collected large multi-institutional ICU databse Artinian V et al. Chest, :

15 Treatment benefit by early standard EN??? (within 24 h of injury or ICU admission) Inclusion: 6 RCTs(234 patients) Doig G. et al. ICM, 2009; 35:

16 Primary analysis: mortality Mortality reduction (OR 0.34; 95% CI ) Reduction in development of pneumonia (OR 0.31; 95% CI ) No reduction in development of MODS

17 Relevant Meta-Analyses: Early EN vs. early PN in the critically ill Group comparison # Studies Years of publication Mortality Infections Braunschweig EN vs. TPN NS TPN EN Heyland EN vs. TPN NS Dhaliwal EN+TPN vs.en NS NS Gramlich EN vs. TPN NS Peter EN vs. TPN NS Simpson EN vs. TPN Heidegger CP et al., Curr Op Crit Care 2008 ; 14:408-14

18 The most effective route for delivery of early nutritional support in critically ill adults???

19 October 1, 2014, at NEJM.org Multicentric PRCT Intervention: EN vs. PN

20 Trial of the route of early nutritional support in critically ill adults: CALORIES-Trial 2388 patients from 33 ICUs ; nutrition started within 36 h (25 kcal/kg BW) for 5 days > PN: 21.3 ± 7.7 kcal/kg -> EN: 18.5 ± 7.7 kcal/kg -> PN (protein): 0.7 ± 0.3 g/kg -> EN (protein): 0.6 ± 0.3 g/kg Harvey SE et al., NEJM 2014; 371(18):

21 Trial of the route of early nutritional support in critically ill adults: CALORIES-Trial 33% Mortality 37% No differences: infections other outcomes adverse events 34% 39% PN group: hypoglycaemia $ vomiting $ PN 8.4 vs. EN 16.2% Harvey SE et al., NEJM 2014; 371(18):

22 CONCLUSIONS No significant difference in 30-day mortality associated with the route of delivery of early nutritional support in critically ill adults. No intrinsic toxicity can be attributed to PN when EN is contraindicated. Harvey SE et al., NEJM 2014; 371(18):

23 Other recent studies What is the optimal timing for PN introduction???

24 The Lancet, 2 February 2013; 381 (9864): Optimisation of energy provision with supplemental parenteral nutrition in critically ill patients: a randomised controlled clinical trial CP. Heidegger1, MM. Berger 2, S. Graf 1,5, W. Zingg 3, P. Darmon 5, MC. Costanza 4, R. Thibault 5, C. Pichard 5 1 Service of Intensive Care, Geneva University Hospital, Switzerland 2 Intensive Care Service, Lausanne University Hospital, Switzerland 3 Infection Control Programme, Geneva University Hospital, Switzerland 4 Department of Mathematics & Statistics, University of Vermont, Burlington, USA 5 Clinical Nutrition, Geneva University Hospital, Switzerland ClinicalTrials.GovN : NCT

25 SPN trial design 2 centre, randomised,controlled, intervention trial, mixed medical & surgical ICUs (Geneva/Lausanne) SPN-group: EN-group: PN at day 3 if EN < 60% energy target EN alone according to local practice

26 «The SPN Study» Kaplan-Meier analysis of the first nosocomial infection p=0.0338* Conclusions Early EN (24 h) + SPN from day 4 to 8 after ICU admission for optimisation of the energy target by PN when EN is insufficient Ł improves clinical outcome in critically ill patients! Nosocomial infections Antibiotic use Time of Mechanical ventilation Heidegger CP et al., Lancet 2013;381 (9864):

27 Contradictory results from another study Impact of Early Parenteral Nutrition Completing Enteral Nutrition in Adult Critically Ill Patients (EPaNIC trial) Casaer MP. et al., NEJM 2011;365(6):506-17

28 The EPaNIC Trial - Outcomes Primary outcome 90-mortality 11,2% Secondary outcomes: morbidity for late PN group Late PN vs. early PN: Discharge alive earlier from ICU & hospital (75,2 vs. 71,7 %). ) ICU infections (22,8 vs. 26,2%) Incidence of cholestasis (p<0.001) MV (36,3 vs. 40,2%; > 2 days on MV) renal replacement therapy (mean reduction of 3 days; p<0.008) Health care costs (Є1,110) Casaer MP. et al., NEJM 2011;365(6):506-17

29 The EPaNIC Trial Conclusions Don t use PN in the critically ill before day 8 after ICU admission Casaer MP. et al., NEJM 2011;365(6):506-17

30 Comparaison EPaNIC vs. SPN trial Patients (n) Cardiac surgery patients (%) EPaNIC ! SPN ICU length of stay: patients 29.8 % (day 7) 96 % (day 9) PN administration Early high glucose load (Gluc 20%) Start at admission All patients regardless of energy supply by EN yes : 400kcal (day1) 800 kcal (day2) On day 4 only if EN <60% of energy target no Calorie target estimated measured by IC Criteria for stopping PN EN>80% of target EN = 100 % of energy target Heidegger CP et al., Lancet 2013;381 (9864):

31 Recent EN & PN delivery PRCTs in ICU patients Take home messages Studies Patients (n) Patients types Practical messages TICACOS Singer et al./2011 EPaNIC Casaer et al./ MV Surgical:45% Medical: 55% 4640 Surgical:89% -> 60% cardiac Medical: 11% Nutritional intervention by IC may be beneficial. Avoid PN in the first 48h of ICU stay, if not indicated. SPN study Heidegger et al./ <60% energy target by day 3 Surgical:46% Medical: 54% Accept low energy EN the first 3 days. Consider PN if EN insufficient on day 4. Singer P. et al., Int Care Med 2011;37:601 9 Casaer MP. et al., NEJM 2011;365(6): Heidegger et al., Lancet 2013; ; 381 (9864):

32 1.372 Australian patients with a temporary contraindication to EN Patients randomized within 24 hours of ICU admission to receive either standard care or early PN Primary endpoint: 60-day mortality Doig G. et al., JAMA 2013;309(20):

33 The Early PN Trial in critically ill patients(n=1372) Nutrition delivery over the first 7 ICU days Patientsreceiving EN or PN each day Energy received per patient by study day Protein received per patient by study day Early PN Early PN Early PN Standard care Standard care Standard care Day-60mortality did not differ significantly: standard care 22.8% vs 21.5% for early PN Outcome benefits for the early PN-group Need for mechanical ventilation (-0.47 days per 10 pat-icu days; p=0.01) Quality of life RAND-36 health status score: better maintenance of muscle mass Doig G. et al., JAMA 2013;309(20):

34 Key messages: No difference in day-60 mortality by provision of early PN to critically ill adults with relative contraindications to early EN vs. standard care. Early PN strategy resulted in significantly fewer days of invasive ventilation but not significantly shorter ICU or hospital stays. No harm was attributed to the use of early PN when contraindications to early EN!! Doig G. et al., JAMA 2013;309(20):

35 Impact of early nutrition & feeding route on Outcomes of MV patients with shock Observational Multicentre Cohort Study <48 h Objective: Association of early nutrition, feeding route & caloric intake to -> mortality -> risk of VAP Early nutrition < 48h post-intubation + invasive MV > 72h + shock state Reignier J. et al., Int Care Med 2015 May;41(5):875-86

36 Timing of nutrition initiation, feeding route, calorie intake on mortality & risk of VAP - with EN In MV patients with shock, early nutrition was associated with mortality. No mortality association with feeding route or early calorie intake. Early nutrition & EN were associated with Æ VAP risk. Benefit from early nutrition, EN or PN in patients with severe critical illnesses!! Reignier J. et al., Intensive Care Med 2015 May;41(5):875-86

37 - Relevant RCTs by electronic search from 1980 to Primary outcome = overall mortality - Secondary outcomes: infectious complications, LOS & MV - Subgroup analyses to examine the treatment effect by: dissimilar caloric intakes year of publication trial methodology Ł inclusion criteria met: 18 RCTs studying 3347 patients Elke et al., Critical Care 2016;20:117

38 Elke et al., Critical Care 2016;20:117

39 Effect of EN vs. PN on Mortality Favours EN Favours PN

40 Effect of EN vs PN on Infectious Complications Favours EN Favours PN

41 Key messages: EN vs. PN Updated meta-analysis on clinical outcomes?? 18 RCTs;3347 randomized critically ill patients No effect on overall mortality EN: $infectious complications (p =0.004) & ICU LOS (p= ) No significant differences in hospital LOS & mechanical ventilation Positive treatment effect of EN vs. PN may be attributed to: differences in caloric intake publication bias among aggregated trials EN = first-line nutritional therapy over PN in critically ill patient!!! Elke et al., Critical Care 2016;20:117

42 ICU nutritional plan priorities Singer P. et al., Curr Op Clin Nutr 2013;16:187-93

43 Conclusions Malnutrition & energy deficit are frequent in ICU patients & worsen outcome Early EN (first 24h) is recommended Stepwise advance of EN within the first 3 days SPN when you cannot achieve the energy goal by EN alone (day 4) De-escalation of PN as soon as possible Avoid under- & overfeeding! Nutritional & metabolic monitoring are mandatory! Don t forget all other rehabilitation tools & therapies!!!

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