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)