2014 Kombinierte enterale und parenterale Ernährung für welche PatientInnen? Dr. CP. Heidegger Intensive Care/Geneva claudia-paula.heidegger@hcuge.ch Bern Freitag, 4. April 2014
Nutrition News Worldwide controversy about optimal amount & route of feeding in critically ill patients. Early EN (24-48h ): standard of care for hemodynamically stable ICU patients with functioning gastrointestinal tract. Place of supplemental PN (SPN)? Conflicting results of recent RCTs of SPN: contradictory or complementary? Recommendation for best clinical practice???
European Guidelines on EN Acute Phase (72-96h): (ESPEN 2006) «All patients who are not expected to be on a full oral diet within 3 days should receive EN» 20 25 kcal/kg/j Post Acute Phase: Severe Undernutrition: 25 30 kcal/kg/j 25 30 kcal/kg/j «Use supplemental PN in patients who cannot be fed sufficiently via the enteral route» Modalities? Outcomes? Kreyman et al., Clin Nutr 2006; 25:210-23
European Guidelines on PN (ESPEN 2009) Indication for supplementary PN All patients receiving less than their targeted enteral feeding after 2 days should be considered for supplementary PN (Grade C) During acute illness, the aim should be to provide energy as close as possible to the measured energy expenditure in order to avoid negative energy balance (Grade B) In the absence of indirect calorimetry, ICU pat. should receive 25kcal/kg/day increasing to target over the next 2-3 days (Grade C) Singer et al., Clin Nutr 2009;28:387-400
US Guidelines on PN (ASPEN 2009 ) Indication for supplementary PN Standard care (intravenous fluids) is recommended first, with PN reserved and initiated only after 7 days in well nourished patients Early PN use (within 24 h of ICU admission) in patients who are malnourished. However, no clear definition of who is malnourished McClave et al., JPEN 2009;33:277-316
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
Picture by M. Donnier/Soins Intensifs-HUG, 2013 Giner et al.; Nutrition 1996; 12:23-9 Kyle et al., Clin Nutr 2006; 25:727-35 Middleton et al., Intern Med J 2001;31:455-481 Martin et al., Can Med Ass J 2004; 170:197-204 Malnutrition & poor outcome in Critically ill patients Malnutrition 20-40% Incidence of complications Infections & MOF Time on MV Mortality ICU & hospital LOS Costs
«A negative energy balance is highly correlated to the occurrence of complications in the ICU» Observational prospective study of 50 mechanically ventilated ICU patients Daily mean energy balance: - 460 kcal/day Mean cumulative energy balance: - 4767kcal Dvir et al., Clin Nutr 2006;25:37-44
Usually feeding practices in the ICU Prospective observational cohort study Average intake 1000 kcal/day BMI<20 BMI 40 BMI 35-40 167 ICUs from 37 countries (5 continents) 2772 mechanically ventilated adult patients ICU stay for 72 hours Data collection: 12 days 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;35:1728-37
TPN negative points? High rate of catheter-related infections especially in central venous lines used for PN But today's standard for CVL have changed: more sterile conditions appropriately trained persons US to identify the vessel Hygiene standard for maintaining CVL Separate lumen for PN The use of peripheral line for PN is more common less infectious complications but: only for 7-10 days
My position in this debate Malnutrition in the critically ill is frequent Energy deficit by EN alone Morbidity & Mortality Optimal & timely calorie/protein delivery in high mortality risk patients by SPN (ICU longstayers) Avoiding Under- and Overfeeding Improves clinical outcomes Metabolic & nutritional monitoring is mandatory Constant adaptation of nutritional requirements Stop SPN as soon as possible
Recent Trials of combined nutrition in the ICU to achieve the energy targets Since 2009
Impact of measuring daily resting energy expenditure by indirect calorimetry as a guide for nutrition support MV patients with ICU stay > 3 days & EN with energy target by: 1) Study group: calorie administration by indirect calorimetry (n=56) 2) Control group: 25 kcal/kg/day rule (n=56) Supplemental PN when required
The TICACOS Study Tight calorie control nutritional support in critically ill patients Kaplan-Meier: Hospital discharge mortality for all patients (ITT; n=130) Study group Trend to improved outcome for hospital LOS & hospital mortality (32.3% vs. 47.7%, p = 0.058) Cumulative energy balance Study gr: 2008 kcal Control gr: -3550 kcal but!!! Infection rate MV Singer P. et al., Int Care Med 2011;37:601 9
The TICACOS Study Tight calorie control nutritional support in critically ill patients Study group: mean daily energy target by indirect calorimetry Measured energy expenditure values during the first 10 days (p<0.008) Overfeeding Singer P. et al., Int Care Med 2011;37:601 9
The TICACOS Study Results Study weakness 1. Single-center pilot study (n=low) 2. Overfeeding by not taking account of non nutritional calories 3. Significant increase in infection rate (incidence of VAP in the study group ; 27.7 vs. 13.8%) => Early & high amount of EN in the study group Singer P. et al., Int Care Med 2011;37:601 9
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
The EPaNIC Trial - Total Energy Levels kcal/kg/d % of target N= 4640 medical-surgical ICU Patients 1. EN & early PN (Early PN group): 20% glucose iv : 400 kcal at day 1; 800 kcal at day 2 PN started at ICU admission day 3 to 100 % calculated energy target Calculated energy target, based on the previous 24 hours EN energy intake EN > 80% or patient on oral intake then PN was stopped (restarted when < 50%) 2. EN only (Late PN group): no PN during the first week of ICU stay if EN is insufficient after 1 week of ICU stay, start PN Casaer MP. et al., NEJM 2011;365(6):506-17
The EPaNIC Trial outcomes Early vs. late PN 90 days survival 11,2% 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
Casaer MP. et al., NEJM 2011;365(6):506-17 The EPaNIC Trial Conclusions Don t use PN in the critically ill before day 8 after ICU admission
The EPaNIC Trial Results Study weakness 1. Study population with predominance of cardiac surgery patients rarely requiring PN (> 60%) 2. Short-stayers: 50% staying < 3 days at day 7: only 30% patients still in ICU 3. No indirect calorimetry for energy assessment 4. High early glucose load in the early PN group Casaer MP. et al., NEJM 2011;365(6):506-17
The Lancet, 2 February 2013; 381 (9864): 385-393 Optimisation of energy provision with supplemental parenteral nutrition in critically ill patients: a randomised controlled clinical trial CP. Heidegger 1, 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.Gov N : NCT00802503
Heidegger CP. et al., ICM 2007;33:963-9 «The SPN Study» Introduction Supplemental PN concept (SPN): Malnourished by EN alone Improved outcome by full energy target Temporary combination of EN & PN (SPN) if energy target <60 % from day 4
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
«The SPN Study» EN and SPN strategies 4 different manufacturers ; 8 different standard products EN: from day 1 Continuous administration (20 to 30 ml/h; max 150 ml/h) Polymeric, fiber-enriched, standard formula Routine protocols (semi-recumbent; nasogastric tubes; prokinetics :GRV > 300 ml) SPN: from day 4 EN & PN 100 % energy needs Energy delivery checked twice daily Central or peripheral PN Protein: >1.2 g/kg/ibw/day (ESPEN guidelines) Both groups: Blood glucose <8.5 mmol/l Trace elements, minerals, and vitamins (ESPEN guidelines) No immune enhancing nutrients
Primary «The SPN Study» Trial endpoints Nosocomial infections between day 9 & 28 (CDC/NHSN surveillance definition of health-care associated infections & criteria for specific types of infections in the acute care settings) Infection categories : 1) Pneumonia (VAP & non-vap; other lower resp. tract infections) 2) Bloodstream infection (laboratory confirmed BSI; clinical sepsis) 3) Urogenital infection 4) Abdominal infection (intra-abdominal) 5) Other infection (skin, bone, soft tissue infections; ear, nose, throat infections; upper resp. and intrathoracic infections) Horan TC. et al., Am J Infect Control 2008;36:309-32
Secondary «The SPN Study» Trial endpoints Antibiotic days & antibiotic-free days (day 1 to 28) Duration of MV (invasive & non-invasive) ICU and hospital LOS until day 28 ICU-,hospital- and global mortality (to day 28) Duration of renal replacement therapy Glycaemia, phosphatemia, CRP & liver tests Drugs (insulin, steroids, antifungal agents)
«The SPN Study» Results
Trial profile «The SPN Study» PP ITT
«The SPN Study» Baseline demographic & clinical characteristics Intention to-treat analysis (n=305) Parameters SPN (n=153) EN (n=152) p - value Age (year) 61 16 60 ± 16 NS Sex (male) 110 (72%) 105(69%) NS BMI (kg/m2) 25 4 26 5 NS APACHE II 22 8 22 7 NS Geneva ICU Lausanne ICU 99 (65%) 54 (35%) 101 (66%) 51 (34%) NS Surgery 70 (46%) 69 (45%) NS Infection at ICU admission(%) 77 (50%) 65 (43%) NS Mean SD, or number (%)
«The SPN Study» Baseline demographic & clinical characteristics Intention to-treat analysis (n=305) Parameters SPN (n=153) EN (n=152) p - value Energy target (kcal/d) 1892 365 1836 388 NS Energy target per IBW (kcal/kg/ibw/day) Protein target (1.2 g/kg/ibw/day) 28 4 27 5 NS 81 7 80 6 NS Indirect Calorimetry at Day 3 in 65% of patients (n=198) *Mean SD, Student t-test
«The SPN Study» Mean protein delivery during intervention (Day 4 to Day 8) Intention to-treat analysis (n=305) Parameter SPN EN (n=153) (n=152) p - value Protein delivery (g/kg/ibw/day) 1.2 0.2 0.8 0.3 < 0.0001 *Mean SD, Student t-test
«The SPN Study» Total Energy Delivery Proportion of energy target provided (%) Mean cumulated energy deficit of -3999±1293 kcal at day 4 103 18% 77 27% p<0.0001 +124±1589 kcal -2317±2657 kcal
«The SPN Study» Kaplan-Meier analysis of the first nosocomial infection p=0.0338* *Statistically significant with Benjamini-Hochberg correction
Clinical Outcome Results: Secondary endpoints Follow-up (days 9-28) & Duration of study (days 1-28) Intention to-treat analysis (n=305)*
«The SPN Study» Other Secondary Outcome Results Intention to-treat analysis (n=305) Parameters SPN (n=153) EN (n=152) p - value Hemofiltration during ICU stay (hours) 52 51 51 45 0.69 Insulin daily dose (UI) Day1 to 3 12 15 14 17 0.31 Day4 to 8 23 24 23 26 0.44 Day4 to 8: number of days Hypoglycaemia (days) 0.2 0.5 0.1 0.3 0.72 Hyperglycaemia (days) 1 1.4 1.1 1.4 0.39 * Data as mean SD. Multivariable linear model adjusted on sex, SAPS II, centre, medical/surgical.
«The SPN Study» Conclusions First RCT to show that optimisation of the energy target by SPN from day 4 to 8 after ICU admission when EN is insufficient improves clinical outcome in critically ill patients Nosocomial infections Antibiotic use Time of Mechanical ventilation Funding sources: This study was supported by grants and research support from: Fond Qualité APSI of the Intensive Care Geneva University Hospital Fondation Nutrition 2000plus Société Nationale Française de Gastroentérologie (SNFGE) Novo Nordisk, France Baxter & Fresenius-Kabi < 25% global budget
Study comparisons'
Patients (n) -Cardiac surgery patients (%) -Emergency admissions EPaNIC 4640 61 42 SPN ICU length of stay: % patients 29.8 (day 7) 96 (day 9) Exclusion of BMI (kg/m2)< 17 Yes No Inclusion only in case of energy deficit (failure of EN) Criteria for SPN Early glucose load 305 13 83 No Yes!!! Independent of energy supply by EN (early PN group) Yes : 400kcal (day1); 800 kcal (day2) EN <60% of energy target Start of PN after ICU admission Within 48 h On day 4 Calorie target Criteria for stopping PN Comparaison EPaNIC vs. SPN trial Calculated EN>80% of target No Indirect calorimetry (2/3 of patients) EN = 100 % of energy target
Comparison of 3 recent PN delivery PRCTs TICACOS EPaNIC SPN Singer P. et al., Curr Op Clin Nutr 2013;16:187-93
Importance of protein targets & outcome Optimal protein & energy nutrition: mortality in mechanically ventilated ICU patients Weijs PJM. et al., JPEN 2012;36:60-68
ICU nutritional plan priorities Singer P. et al., Curr Op Clin Nutr 2013;16:187-93
Conclusions Malnutrition & energy deficit are frequent in ICU patients Early EN is recommended for the critically ill Consider SPN when you cannot achieve the energy targets by EN alone after 3 days De-escalation of PN as soon as EN is reaching the goals Avoid under- and overfeeding Glycaemia control is mandatory! Don t forget all other rehabilitation tools and therapies!!!