Nutrition ICU Fellowship Training Radboudumc
Critical Care MCQ s Nasogastric (NG) and nasojejunal (NJ) feeding tubes: A. Enteral nutrition is associated with a reduced risk of bacterial and toxin translocation. B. Gastric residual volumes of 200ml increases the risk of reflux/aspiration and feeding should be stopped. C. NJ feeding is indicated post-gastro-oesophageal surgery. D. NG tubes should not be passed further than 65cm. E. NJ tubes are easily placed.
Critical Care MCQ s Regarding critical care nutrition: A. Commencing enteral nutrition within 24 hours of intensive care admission is associated with a significant reduction in mortality. B. Trophic feeding compared to full feeding during the first week of intensive care admission, is associated with worse functional outcomes in patients with acute lung injury. C. During the early phase of critical care, a protein intake (0,5g/kg/day) is recommended. D. Selenium supplementation is of no benefit in septic patients. E. The timing of parenteral nutrition prescription remains uncertain.
Critical Care MCQ s Nutritional requirements: A. The Parkland formula is used to predict caloric requirements. B. 25-30kcal/kg/day is the estimated daily energy requirement. C. The typical daily sodium requirement is 0,7-1mmol/kg/day. D. The typical daily carbohydrate requirement is 3-4g/kg/day, of which 60% should be glucose in parenteral nutrition. E. The typical daily calcium requirement is 0,4mmol/kg/day.
Critical Care MCQ s Vitamins and amino acids: A. A non-essential amino acids is one that cannot be synthesized and must be supplied in diet. B. In patients with severe organ failure, it is recommended that the non-essential amino acid, glutamine, is started within the first 24 hours of intensive care unit admission. C. 700-900mg is the recommended daily allowance for vitamin C. D. Thiamine deficiency may cause wet beri-beri. E. Rebound hypoglycaemia may occur on cessation of parenteral nutrition.
Nutrition. 4 essential questions: Why should we take the time to optimize nutrition? Which is the preferred route? Enteral vs Parenteral? What about the timing? Enteral feeding vs SPN? Are supplements beneficial? Special considerations?
Introduction Protein/calorie malnutrition is very frequent in critically ill patients Protein/calorie malnutrition is associated with a worse outcome In approximately 10-15% of patients early enteral nutrition is either contraindicated or not tolerated
Major trials all show underfeeding Singer P. Intensive Care Med 2015;41:154-156
Nutrition support research Enteral vs Parenteral nutrition - Difficult to interpret due to the challenges achieving adequate study size and quality. - However, in a variety of patient populations, the preponderance of data supports the benefits of choosing EN over PN when patients require nutrition support. Seres DS. Therap Adv Gastroenterol. 2013 Mar; 6(2): 157 167.
Early enteral nutrition Meta-analysis Primary analysis - Total (95% 119 115 100.00 0.34 [0.14, Doig GS. Intensive Care Med 2009;35:2018-2027
However... TPN has multiple side-effects
Guidelines based on expert opinion ESPEN: consider after two days ASPEN: consider after seven days if no malnutrition present
EPaNIC trial Multicenter RCT comparing early start SPN (D3) versus late start (D8) Adult ICU patients nutritionally at risk (NRS > 2) but not chronically malnourished (BMI 17) Stratification according to 16 diagnostic categories and randomisation 1:1 Primary endpoint: duration of ICU dependency Casaer MP. NEJM 2011
Enrollment
Early and late group Early: glucose 20% (D1 400 kcal and D2 800 kcal) - D3 start additional SPN to reach calculated nutritional target - diminished/stop when 80% of target covered by EN - restarted when EN < 50% Late: D1 -D7 glucose 5% and SPN added on D8 if EN was insufficient to reach calculated target Both groups EN started on D2 with standing orders
Results Study groups perfectly matched - sepsis 22% and mean APACHE II 23. However mostly postoperative cardiac surgery with short ICU stay As expected patients in the early SPN group needed higher mean daily insulin levels to reach target glucose levels
Predefined subgroup analysis Risk of infection much lower in late SPN group when EN contraindicated for the first 7 days
Secondary analysis No benefit of early SPN in more severely ill patients Risk of later discharge increases with amount of macronutrients Casaer MP. AJRCCM 2013
= more sick medical patients
EDEN trial Multicenter open label trial in ARDSnet hospitals - stratification by site and presence of shock Trophic versus full EN for the first 6 days of mechanical ventilation ALI < 48 hours and MV < 72 hours. No data on preexistent malnutrition. Severe malnutrition excluded ARDSnet. JAMA 2012
Enrollment
Trophic and full EN strategy Started within 6 hours after enrollment and continued until D6, extubation or death - after D6 full EN - glucose 4-8 mmol/l Trophic: 10-20 kcal/h (first 272 patients), the rest 20 kcal/hour Full: see algorithm - goal 25-30 non-protein calories/kg/day and 1.2-1.6 gr/kg protein
Endpoints Primary: VFD's through D28 Multiple secondary endpoints No baseline differences between groups APACHE III score 90
Caloric intake
Gastro-intestinal intolerance
VFD's through Day 28 20 15 14,9 15 Days 10 5 0 Trophic Full
60-day mortality 25 20 23,2 22,2 15 % 10 5 0 Trophic Full Other secondary endpoints no differences also when analysed by BMI
Other results Higher glucose levels and insulin dose in Full group More positive fluid balance in Full group
Heidegger trial RCT in two mixed medical/surgical ICU's (tertiary care university hospitals) Inclusion if after D3 < 60% of nutritional needs were covered by EN AND expected to stay more than 5 days AND functional GI tract 1:1 randomization stratified for sex and admission category (medical/surgical) Heidegger CP. Lancet 2013
Nutrition scheme
SPN and EN group All patients started on D1 with EN (goal males 30 kcal/kg IBW, females 25 kcal/kg IBW - protein 1.2 gr/kg) SPN: started on D4 - continued for 5 days - energy requirement determined by indirect calorimetry. No glutamine etc. In both groups glucose < 8.5 mmol/l
Enrollment Primary outcome: nosocomial infection from D9 - D28
Results No differences in baseline characteristics Apache II 23 Indirect calorimetry in only 65% Protein delivery D4 - D8 1.2 gr/kg in SPN and 0.8 gr/kg in EN group
Nosocomial infections 40 38 30 27 20 10 0 EN TPN supplement P = 0.034 More antibiotic free days in TPN group
Kaplan- Meier
Individual infections No differences in LOS or mortality
Conclusions (1) Initiation enteral feeding Before start evaluate recent weight loss, disease severity, function GI tract (Gr E) EN is the preferred route of feeding (Gr B) EN should be started within 24-48 hours (Gr C)
Conclusions (2) Initiation enteral feeding EN should be withheld during initial resuscitation for hemodynamic instability (Gr E) For the initiation of EN presence of bowel sounds or passage of stools is unnecessary (Gr B) Gastric and small bowel feeding are both acceptable. With gastric retention small bowel feeding is indicated (Gr C)
Conclusions (3) Dosing enteral feeding At the start define target goal preferentially with indirect calorimetry (Gr C) At least 65% of nutritional goals are required < 1 week to achieve clinical benefit of EN (Gr C) Protein 1.2-2 g/kg actual BW (Gr E) With morbid obesity hypocaloric feeding (60-70% of target / 22-25 kcal/kg IBW) with high protein content 2-2.5 g/kg IBW (Gr D)
Conclusions (4) Early EN and SPN In previously non- malnourished patients it is save AND probably better to withhold SPN for the first 7 days if EN is insufficient to meet caloric needs in most patient groups Uncertainty for the most severely ill (e.g persistent high SOFA). If full EN appears impossible for 7 days, SPN on D4 is reasonable If enteral nutrition is absolutely contraindicated for more than 7 days, starting TPN on D4 is reasonable In case of preexistent severe malnutrition (BMI < 17) AND inability to reach nutritional targets with EN on D4, starting SPN is reasonable
Vincent JL. Lancet 2013
CALORIES trial RCT (MC - adults) early EN vs PEN in unplanned admissions (start < 36 hrs) Patients > 18 years expected to require nutritional support for at least 2 days Exclusively for 5 D, until ICU discharge or death Energy target 25 kcal/kg Harvey SE. N Engl J Med 2014;371:1673-1684
Clinical outcome P = 0.57 P = 0.40 P = 1.00 P = 0.006 P < 0.001 40 30 % 20 10 0 30-D mortality 90-D mortality SAE Hypoglycemia Vomiting Harvey SE. N Engl J Med 2014;371:1673-1684
Supplements Glutamine Anti-oxidants: selenium, zinc, beta carotene, Vitamins E and C Essential fatty acids: Omega-3, GLA (y-linolecacid)
Glutamine at ICU admission Glutamine > 420 μmol/l Glutamine < 420 μmol/l 50 P = 0.037 All-cause 6-month mortality 40 30 20 10 28 43 0 N = 174 Rodas PC. Clinical Science 2012
Glutamine SIGNET study Multi-centre trial (N=10) Adults with expected LOS 48 hrs with 50% of nutritional requirements by PN 2 2 factorial design. Allocation to one of four isocaloric,iso-nitrogenous groups: glutamine, selenium, both or no additional glutamine or selenium: 7 days ICU, continuation on subsequent wards if practicable Andrews PJD. BMJ 2011;342:d1542
Glutamine N = 502 SIGNET study New infections Mortality ICU Mortality 6 M 60 60 45 45 % 30 % 30 15 15 0 Glutamine Selenium Both Neither 0 Any glutamine Any selenium 126 127 124 125 For patients treated > 5 days selenium reduced the number of new infections No differences in secondary outcomes Andrews PJD. BMJ 2011;342:d1542
Scandinavian glutamine trial Multi-centre placebo-controlled RCT (N=11) Adult ICU patients with EN/TPN within 72 hours after ICU admission 0.283 g glutamine/kg/day versus placebo for complete ICU period Analysis per protocol (> 3 days) and ITT Wernerman J. Acta Anaesthesiol Scand 2011;55:812-818
Scandinavian glutamine trial N = 413 Placebo Glutamine 40 40 P = 0.368 P = 0.646 30 P = 0.0456 P = 0.0976 30 Mortality (%) 20 Mortality (%) 20 10 10 0 16,2 9,3 16,6 10,8 Per protocol ITT 0 34,6 31,2 32,6 34,2 Per protocol ITT ICU mortality 6 M mortality Primary outcome: change in SOFA D1 - D7 in PP group - no differences Wernerman J. Acta Anaesthesiol Scand 2011;55:812-818
A Randomized Trial of Glutamine and Antioxidants in Critically Ill Patients MC RCT (40) with 2 2 design (glutamine and antioxidant supplementation for 28 D) Inclusion criterium: mechanical ventilation + organ failures Primary outcome: 28-day mortality Glutamine 0.35 mg/kg IBW Antioxidants: selenium, zinc, beta carotene, Vitamins E and C Heyland D. N Engl J Med 2013
Glutamine supplement Glutamine No glutamine Antioxidants No antioxidants 40 P = 0.05 P = 0.48 40 % 30 20 32,4 27,2 % 30 20 30,8 28,8 In-hospital mortality Secondary outcomes Glutamine No glutamine P-value 37.2% 31% 0.02 10 10 6 M mortality 43,7% 37,2% 0.02 0 Mortality 28 D 0 Mortality 28 D Urea 13,4% 4% < 0.001 No interaction between glutamine and antioxidants N = 1218 Heyland D. N Engl J Med 2013
Subgroup analysis Heyland D. N Engl J Med 2013
INTERSEPT study Omega-3, GLA, anti-oxidants (Oxepa ) N = 106 Pontes-Arruda A. Crit Care 2011;15:R144
INTERSEPT study Primary Outcome Pontes-Arruda A. Crit Care 2011;15:R144
INTERSEPT study Organ Failure and Mortality 30 20 % 10 0 28 D Mortality Benefits of Oxepa is only proven in critically ill patients with early sepsis without organ failure Pontes-Arruda A. Crit Care 2011;15:R144
Omega-3, γ-linolenic acid and antioxidants A randomized, double blinded, placebo-controlled, MC trial (N=44) Patients with ALI (<48h) requiring mechanical ventilation and planned for EN Twice-daily enteral supplementation with N-3 FA, GLA and anti-oxidants or placebo either 21 days or until extubation 2 2 factorial design - low - vs full-calorie EN Rice TW. JAMA 2011;306:1574-1581
Omega-3, γ-linolenic acid and antioxidants N = 272 Stopped for futility 28 Omega 3 Placebo P = 0.02 P = 0.04 P = 0.054 21 14 7 0 Ventilator Free Days ICU Free Days Mortality (%) Rice TW. JAMA 2011;306:1574-1581
Special considerations Nutrition and ARF / CRRT
Special considerations Nutrition and ARF / CRRT Also Thiamine 100 mg/d Citrate and lactate deliver up to 500 kcal/day Wiesen P. JPEN 2011;35:217-222