Question 9

College answer

Evidence

• No clear evidence that early commencement of enteral nutrition within the first week improves outcomes
  • Notable trials:
    • EDEN (JAMA 2012, ARDSNET Investigators) Full enteral feeds vs “trophic” showed equivalent “hard” outcomes and “trophic” did better in terms of reflux, BSL control and had negative fluid balance
    • PERMiT (NEJM 2015, Saudi Arabia) 50% vs 100% caloric intake showed very similar results
    • No evidence for early supplementation with TPN (EPaNIC trial)
    • More recently TARGET (ANZICS 2017) showed no outcome difference between 1.5 and 1.0 kcal/mL feeds in an unselected ICU population (burns excluded), but more hyperglycaemia and upper GI effects in the 1.5 kcal/mL group (4,000 patients)

Note: TARGET was not examining timing of feeds but may be mentioned in the context of reduced caloric intake showing similar outcomes.

• Trophic feeding for gut integrity and health (25% calories) delivered enterally improves outcomes in many groups, most notably pancreatitis

Summary Statement

Allow hypocaloric feeding for up to 7 days in previously well-nourished patients Early provision of vitamin and trace element supplementation

Examiners Comments:

Generally, well answered question. Most candidates were able to give reasonable responses to the questions addressing the important issues. Those that failed were unable to state why early feeding may be important and describe advantages/disadvantages or unable to discuss evidence around the topic.

Discussion

Rationale and definition:

• Early nutrition is defined as nutrition provided within the first 48 hours of ICU stay
• This window is characterised by:
  • Hypercatabolic state and increased requirement for macro/micronutrients
  • Decreased gut health and increased need for trophic stimulus
  • A greater susceptibility of the patient to the added insults of gut bacterial translocation and malnutrition
• The rationale for providing early nutrition during this period is:
  • A critically ill patient has increased energy requirements
  • Their gut health is compromised because of shock and the stress response state
  • Mucosal integrity is compromised and bacterial translocation may occur
  • Delaying nutrition produces the risk of refeeding syndrome once nutrition is eventually reintroduced
  • Early nutrition addresses these specific concerns

Advantages:

• Maintained delivery of macro and micronutrients
• Defence of gut flora and intestinal mucosal integrity
• Prevent refeeding syndrome
• Treatment for any sort of underlying malnutrition
• Enteral is safer than parenteral nutrition

Disadvantages

• May be poorly tolerated (in terms of high residual gastric volumes); risk of aspiration
• May not be absorbed (oedematous or poorly perfused intestine)
• Diarrhoea and abdominal distension may develop
• Total body utilisation of these nutrients may not be normal; we don't know what nutrient dose these patients need
• There is no evidence that early 100%-of-goal nutrition actually prevents muscle catabolism
• The hypercatabolic stress response is adaptive, and working against it may be counterproductive

• Together with the stress response, hyperglycaemia may result, which has many disadvantages in the critically ill
• Trials tend to focus on high risk critically ill patients with high illness severity, excluding the routine low-risk patients (i.e. these probably will not benefit)
• Parenteral route has a host of unique complications (LFT derangement, infection risk, etc)

Evidence in support of early nutrition

• There does not appear to be any harm from early nutrition (Heighes et al, 2016).
• Meta-analysis suggests a decreased risk (RR 0.76) for infectious complications, but only when non-ICU patients were included (ESPEN)
• The evidence seems to support early enteral nutrition rather than parenteral, particularly with respect to infectious complications
• There is good evidence that "trophic feeding" is beneficial, i.e. early nutrition need not be targeting a full goal rate

Evidence against early nutrition

• None of the RCT studies have ever demonstrated a mortality benefit from early nutrition
• Many studies have demonstrated that hyperglycaemia has a significant association with increased mortality and morbidity in the ICU
• When used in shocked patients, early enteral nutrition may increase the risk of gut ischaemia (Reignier et al, 2018)

These "notable trials" which the trainees should probably know:

• EDEN (Rice et al, 2012)
• PERMiT (Arabi et al, 2015)
• EPaNIC (Casaer et al, 2011)
• TARGET (ANZICS CTG, 2018)

Rice, Todd W., et al. "A randomized trial of initial trophic versus full-energy enteral nutrition in mechanically ventilated patients with acute respiratory failure." Critical care medicine 39.5 (2011): 967.

Heighes, Philippa T., Gordon S. Doig, and Fiona Simpson. "Timing and Indications for Enteral Nutrition in the Critically Ill." Nutrition Support for the Critically Ill. Springer International Publishing, 2016. 55-62.

McClave, Stephen A., et al. "Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (ASPEN)." Journal of Parenteral and Enteral Nutrition 40.2 (2016): 159-211.

Mentec, Hervé, et al. "Upper digestive intolerance during enteral nutrition in critically ill patients: frequency, risk factors, and complications." Critical care medicine 29.10 (2001): 1955-1961.

Heyland, Daren K., et al. "Canadian clinical practice guidelines for nutrition support in mechanically ventilated, critically ill adult patients." Journal of Parenteral and Enteral nutrition 27.5 (2003): 355-373.

Montejo, J. C., et al. "Gastric residual volume during enteral nutrition in ICU patients: the REGANE study." Intensive care medicine 36.8 (2010): 1386-1393.

Poulard, Fanny, et al. "Impact of Not Measuring Residual Gastric Volume in Mechanically Ventilated Patients Receiving Early Enteral Feeding A Prospective Before–After Study." Journal of Parenteral and Enteral Nutrition 34.2 (2010): 125-130.

Desachy, Arnaud, et al. "Initial efficacy and tolerability of early enteral nutrition with immediate or gradual introduction in intubated patients." Intensive care medicine 34.6 (2008): 1054-1059.

Juvé-Udina, Maria-Eulàlia, et al. "To return or to discard? Randomised trial on gastric residual volume management." Intensive and Critical Care Nursing 25.5 (2009): 258-267.

Bing, Guo. "Gastric residual volume management in critically ill mechanically ventilated patients: A literature review." Proceedings of Singapore Healthcare (2015): 2010105815598451.

Nguyen, Nam Q. "Pharmacological therapy of feed intolerance in the critically ills." World journal of gastrointestinal pharmacology and therapeutics 5.3 (2014): 148.

Marino, L. V., et al. "To determine the effect of metoclopramide on gastric emptying in severe head injuries: a prospective, randomized, controlled clinical trial." British journal of neurosurgery 17.1 (2003): 24-28.

Nguyen, Nam Q., et al. "Erythromycin is more effective than metoclopramide in the treatment of feed intolerance in critical illness*." Critical care medicine 35.2 (2007): 483-489.

Fraser, R. J., A. M. Deane, and Marianne J. Chapman. "Prokinetic drugs for feed intolerance in critical illness: current and potential therapies." Critical Care and Resuscitation 11.2 (2009): 132.

Singer, Pierre, et al. "ESPEN guidelines on parenteral nutrition: intensive care." Clinical nutrition 28.4 (2009): 387-400.

van Zanten, Arthur RH, et al. "Enteral glutamine supplementation in critically ill patients: a systematic review and meta-analysis." Critical Care 19.1 (2015): 1-16.

Oldani, Massimo, et al. "Glutamine Supplementation in Intensive Care Patients: A Meta-Analysis of Randomized Clinical Trials." Medicine 94.31 (2015).

Wernerman, Jan. "How to understand the results of studies of glutamine supplementation." Critical Care 19.1 (2015): 1-3.

van Zanten, Arthur RH, Zandrie Hofman, and Daren K. Heyland. "Consequences of the REDOXS and METAPLUS Trials The End of an Era of Glutamine and Antioxidant Supplementation for Critically Ill Patients?." Journal of Parenteral and Enteral Nutrition (2015): 0148607114567201.

Heyland, Daren, et al. "A randomized trial of glutamine and antioxidants in critically ill patients." New England Journal of Medicine 368.16 (2013): 1489-1497.

Van Zanten, Arthur RH, et al. "High-protein enteral nutrition enriched with immune-modulating nutrients vs standard high-protein enteral nutrition and nosocomial infections in the ICU: a randomized clinical trial." Jama 312.5 (2014): 514-524.

Ridley, Emma, Dashiell Gantner, and Vincent Pellegrino. "Nutrition therapy in critically ill patients-a review of current evidence for clinicians." Clinical Nutrition 34.4 (2015): 565-571.

Singer, Pierre, et al. "The tight calorie control study (TICACOS): a prospective, randomized, controlled pilot study of nutritional support in critically ill patients." Intensive care medicine 37.4 (2011): 601-609.

Casaer, Michael P., et al. "Early versus late parenteral nutrition in critically ill adults." N Engl J Med 365.6 (2011): 506-517.

Heidegger, Claudia Paula, et al. "Optimisation of energy provision with supplemental parenteral nutrition in critically ill patients: a randomised controlled clinical trial." The Lancet 381.9864 (2013): 385-393.

Doig, Gordon S., et al. "Early parenteral nutrition in critically ill patients with short-term relative contraindications to early enteral nutrition: a randomized controlled trial." Jama 309.20 (2013): 2130-2138.

Davies, Andrew R., et al. "A multicenter, randomized controlled trial comparing early nasojejunal with nasogastric nutrition in critical illness*." Critical care medicine 40.8 (2012): 2342-2348.

Harvey, Sheila E., et al. "Trial of the route of early nutritional support in critically ill adults." New England Journal of Medicine 371.18 (2014): 1673-1684.

Andrews, Peter JD, et al. "Randomised trial of glutamine, selenium, or both, to supplement parenteral nutrition for critically ill patients." Bmj 342 (2011): d1542.

Vassilyadi, Frank, Alkistis-Kira Panteliadou, and Christos Panteliadis. "Hallmarks in the History of Enteral and Parenteral Nutrition From Antiquity to the 20th Century." Nutrition in Clinical Practice 28.2 (2013): 209-217.

Tian, Feng, et al. "Effect of initial calorie intake via enteral nutrition in critical illness: a meta-analysis of randomised controlled trials." Crit Care 19 (2015): 180.

Jeejeebhoy, Khursheed N. "Nutrition Needs Should Be Modified to Consider Nutrition Status and Acuity of Illness Lessons From the INTACT Trial." Journal of Parenteral and Enteral Nutrition 40.1 (2016): 10-11.

Marik, Paul E., and Michael H. Hooper. "Normocaloric versus hypocaloric feeding on the outcomes of ICU patients: a systematic review and meta-analysis." Intensive care medicine (2015): 1-8.

Rice, Todd W., et al. "A randomized trial of initial trophic versus full-energy enteral nutrition in mechanically ventilated patients with acute respiratory failure." Critical care medicine 39.5 (2011): 967.

Arabi, Yaseen M., et al. "Permissive Underfeeding or Standard Enteral Feeding in High–and Low–Nutritional-Risk Critically Ill Adults. Post Hoc Analysis of the PermiT Trial." American journal of respiratory and critical care medicine 195.5 (2017): 652-662.

Casaer, Michael P., et al. "Early versus late parenteral nutrition in critically ill adults." New England Journal of Medicine 365.6 (2011): 506-517.

TARGET Investigators, for the ANZICS Clinical Trials Group. "Energy-Dense versus Routine Enteral Nutrition in the Critically Ill." New England Journal of Medicine 379.19 (2018): 1823-1834.

Reignier, Jean, et al. "Enteral versus parenteral early nutrition in ventilated adults with shock: a randomised, controlled, multicentre, open-label, parallel-group study (NUTRIREA-2)." The Lancet 391.10116 (2018): 133-143.