Nutrition Literature Summaries

OVERVIEW

• summaries of key studies from the intensive care nutrition literature
• at present the best advice is to optimize oral/enteral nutrition, avoid forced starvation if at all possible, and judiciously use supplemental parenteral nutrition
• supplementation of nutrition with glutamine should not be routine (increased mortality in Heyland study 2013)

TROPHIC FEEDING

EDEN study:

National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome  (ARDS) Clinical Trials Network, Rice TW, Wheeler AP, Thompson BT, Steingrub J, Hite RD, Moss M, Morris A, Dong N, Rock P. Initial trophic vs full enteral feeding in patients with acute lung injury: the EDEN randomized trial. JAMA. 2012 Feb 22;307(8):795-803. PMC3743415.

• open label MC RCT
• 1000 adults requiring mechanical ventilation for acute lung injury, within 48 hours of onset
• full enteric feeding versus trophic feeding only for the first 6 days
• no difference in 60d mortality, pneumonia or diarrhoea

EARLY PARENTAL NUTRITION

EPN trial:

Doig G, et al. Early Parenteral Nutrition in Critically Ill Patients With Short-term Relative Contraindications to Early Enteral Nutrition: A Randomized Controlled Trial. JAMA 2013; epublished May 20th

• single-blinded MCRCT
• n = 1372
• early parenteral nutrition (PN) in critically ill adults with relative contraindications to early enteral nutrition (EN)(n=686) with standard care (n=686)
• Intervention:
  — Patients receiving early PN started PN a mean of 44 minutes after enrollment (95% CI 36 to 55)
• Control:
  — Of 682 patients receiving standard care, 199 patients (29.2%) initially commenced EN, 186 patients (27.3%) initially commenced PN, and 278 patients (40.8%) remained unfed
  — Time to EN or PN in patients receiving standard care was 2.8 days (95% CI, 2.3 to 3.4)
• Primary uutcome:
  — no difference in 60 day mortality (standard care 22.8% versus early PN 21.5%; risk difference −1.26%; 95% CI −6.6 to 4.1; P = 0.60)
• Secondary outcomes:
  — no difference in ICU or hospital length of stay (LOS)
  — Early PN patients rated 60 day quality of life (RAND-36 General Health Status) statistically higher, but not clinically meaningful
  — Early PN patients required fewer days of invasive ventilation (7.73 vs 7.26 days per 10 patient × ICU days, risk difference −0.47; 95% CI, −0.82 to −0.11; P = 0.01)
  — Early PN patients based on Subjective Global Assessment, experienced:
  less muscle wasting (0.43 vs 0.27 score increase per week; mean difference −0.16; 95% CI −0.28 to −0.038; P = 0.01)
  and fat loss (0.44 vs 0.31 score increase per week; mean difference −0.13; 95% CI −0.25 to −0.01; P = 0.04)
• Commentary/ criticisms:
  — highly select group
  — standard care patients often had wait 3 or more days to be fed, earlier EN may have been better
  — would PN benefits be greater if it was used more frequently (e.g. greater familiarity)?

EPaNIC trial: Casaer MP, Mesotten D, Hermans G, Wouters PJ, Schetz M, Meyfroidt G, Van Cromphaut S, Ingels C, Meersseman P, Muller J, Vlasselaers D, Debaveye Y, Desmet  L, Dubois J, Van Assche A, Vanderheyden S, Wilmer A, Van den Berghe G. Early versus late parenteral nutrition in critically ill adults. N Engl J Med. 2011 Aug 11;365(6):506-17. PMID: 21714640.

• MC RCT
• 4640 pateints
• intervention: early PN (started day 2)
• control: late PN (started day 8)
• outcomes: no mortality difference (ICU or 90 days), but decreased infection, cholesatis, mechanical ventilation, RRT and ICU LOS
• commentary and criticisms:
  — a shambles — why would the patients included in this study need PN!
  — short stay patients (39% less than 3 days in ICU) and cardiothoracic surgery patients (61%)
  — did not follow ESPEN guidelines (i.e. only start PN after EN fails) and patients lacked indication for PN
  — energy targets were not confirmed by indirect calorimetry
  — patients with BMI <18.5 were excluded (the ones most likely to benefit from PN!)

SPN trial: Heidegger CP, Berger MM, Graf S, Zingg W, Darmon P, Costanza MC, Thibault R, Pichard C. Optimisation of energy provision with supplemental parenteral nutrition in critically ill patients: a randomised controlled clinical trial. Lancet. 2013 Feb 2;381(9864):385-93. PMID: 23218813.

• Swiss 2 center RCT
• 305 patients in ICU for at least 5 days who failed to reach 60% of target from enteral nutrition at day 3
• control: enteral nutrition according to ESPEN guidelines
• intervention: supplemental PN to meet 100% of target at days 4 to 8
• outcomes: decreased infections, increased antibiotics, decreased time on mechanical ventilation

TARGETED ENERGY DELIVERY

TICACOS Trial: Singer P, Anbar R, Cohen J, Shapiro H, Shalita-Chesner M, Lev S, Grozovski E,  Theilla M, Frishman S, Madar Z. The tight calorie control study (TICACOS): a prospective, randomized, controlled pilot study of nutritional support in critically ill patients. Intensive Care Med. 2011 Apr;37(4):601-9. PMID: 21340655.

• Pilot RCT
• 112 patients enterally fed with indirect calorimetry performed
• control: 25 kcal/kg/d fixed rate of energy provision
• intervention: target adapted according to indirect calorimetry results
• outcomes: post-ICU mortality benefit, increased energy and protein delivery in the intervention arm
• commentary and criticisms:
  — small study
  — non-nutritional energy sources not considered , hence all patients systematically overfed
  — although deeply flawed, first study to show mortality befit from optimising enteral nutrition

NASOGASTRIC VERSUS NASOJEJUNAL ROUTE

ENTERIC Study: Davies AR, Morrison SS, Bailey MJ, Bellomo R, Cooper DJ, Doig GS, Finfer SR, Heyland DK; ENTERIC Study Investigators; ANZICS Clinical Trials Group. A multicenter, randomized controlled trial comparing early nasojejunal with nasogastric nutrition in critical illness. Crit Care Med. 2012 Aug;40(8):2342-8. PMID: 22809907.

• ANZICS MC RCT
• 181 patients with increased gastric residual volumes at 72 hours
• Placement of frictional nasojejunal tube versus nasogastric feeding
• Primary outcome: no difference in energy delivered
• Secondary outcomes: increase in minor GI bleeding, no difference in 60d mortality, pneumonia or diarrhoea

GLUTAMINE SUPPLEMENTATION

Heyland D, Muscedere J, Wischmeyer PE, Cook D, Jones G, Albert M, Elke G, Berger MM, Day AG; Canadian Critical Care Trials Group. A randomized trial of glutamine and antioxidants in critically ill patients. N Engl J Med. 2013 Apr 18;368(16):1489-97. PMID: 23594003.

• blinded 2×2 factorial trial
• 1223 patients
• patients had multiorgan failure and were receiving mechanical ventilation
•  supplements of glutamine vs antioxidants vs both vs placebo only
• primary outcome was 28-day mortality
  -> antioxidants -> no difference
  -> glutamine -> strong trend to increased mortality at 28d; significant increase in in-hospital and 6 month mortality
• contradicts the Garrel 2003 study of severe burns patients receiving glutamine
• commentary/ criticisms:
  — was glutamine dose appropriate?
  — should glutamine be restricted to patients with low glutamine levels?

Garrel, D. et al (2003) ‘Decreased mortality and infectious morbidity in adult burn patients given enteral glutamine supplements: a prospective, controlled, randomized clinical trial’ Critical Care Medicine, 31:2444-2449

• double-blinded RCT
• n = 45
• severe burns
• glutamine-enriched enteral nutrition vs isonitrogenous controlled mixture until complete wound healing occurred
• significant reduction in mortality in glutamine group
• reduction in infectious complications

GUIDELINES

Heyland, DK. et al (2003) ‘Canadian Critical Care Practice Guidelines Committee. Canadian clinical practice guidelines for nutrition support in mechanically ventilated, critically ill patients.’ Journal of Parenteral Enteral Nutrition 27:355-373

• series of systematic reviews looking at a range of nutritional questions
  -> EN over TPN whenever possible:
  -> reduced infections
  -> no change in mortality
  -> early commencement of EN within 24-48 hours using a standard polymeric formula

• insufficient evidence for: role of indirect calorimetry, the pH of EN, continuous vs bolus, feeding, probiotics
• risks of TPN (lipid delivery -> immune suppression and ARDS)

ANZICS Clinical Trial Group “The Effect of Evidence–Based Feeding Guidelines on Mortality of Critically Ill Adults: A Cluster Randomised Controlled Trial” JAMA 2008;300(23) 2731-2741

• cluster RCT
• 27 ICU’s
• Australia and NZ
• November 2003 -> May 2004
• n = 1118
• patients expected to stay in ICU > 2 days
  -> guidelines group – fed earlier, achieved caloric goals more often
  -> no difference in hospital discharge mortality, hospital length of stay or ICU length of stay

References and Links

• ANZICS Clinical Trial Group “The Effect of Evidence–Based Feeding Guidelines on Mortality of Critically Ill Adults: A Cluster Randomised Controlled Trial” JAMA 2008;300(23) 2731-2741
• Berger MM, Pichard C. Best timing for energy provision during critical illness. Crit Care. 2012 Dec 12;16(2):215. doi: 10.1186/cc11229. PubMed PMID: 22429787.
  Doig G, et al. Early Parenteral Nutrition in Critically Ill Patients With Short-term Relative Contraindications to Early Enteral Nutrition: A Randomized Controlled Trial. JAMA 2013; epublished May 20th
• Heyland, DK. et al (2003) ‘Canadian Critical Care Practice Guidelines Committee. Canadian clinical practice guidelines for nutrition support in mechanically ventilated, critically ill patients.’ Journal of Parenteral Enteral Nutrition 27:355-373
• Heyland D, Muscedere J, Wischmeyer PE, Cook D, Jones G, Albert M, Elke G, Berger MM, Day AG; Canadian Critical Care Trials Group. A randomized trial of glutamine and antioxidants in critically ill patients. N Engl J Med. 2013 Apr 18;368(16):1489-97. doi: 10.1056/NEJMoa1212722. PubMed PMID: 23594003.
• Ochoa Gautier. Early Nutrition in Critically Ill Patients: Feed Carefully and in Moderation. JAMA 2013; epublished May 20th