Hypocaloric enteral nutrition

Question 23 from the first paper of 2017 asked for a substantial amount of detail with regards to permissive undefeeding, hypocaloric entral nutrution and trophic feeding. Having discussed the importance of good nutrition over many chapters, the author acknowledges that there is an argument to be made for intentionally underfeeding ICU patients. 

In brief summary:

• Hypocaloric nutrition is defined as nutrition which intentionally delivers less nonprotein nutrients than would be required for daily energy expenditure.
• Trophic feeding is defined as feeding at a rate under 500 kcal/day 
• Permissive underfeeding  is defined as as feeding under 40-60% of the calories required for daily energy expenditure.
• The difference between "trophic" and "permisive" hypocaloric nutrition is that the intention of "permissive underfeeding" is to intentionally provide less nutrition, whereas "trophic" feeding does not have nutrition as its goal and instead focuses on maintaining gut integrity.

 Good reading for this topic should start with  Josh Farkas' entry in Pulmcrit, and - for most of us- it should finish there as well. To scrape the world literature for meaningful information is something the time-poor candidate cannot afford, and Farkas' article has the benefit of being written in human-readable language. 

Hypocaloric nutrition

Hypocaloric nutrition is a nutritional strategy which intentionally restricts the amount of intake. Specifically, the term "hypocaloric" implies that only energy intake is decreased, and protein or fat macronutrients may still meet metabolic needs. This is not new, nor unique to intensive care. It is a fashion trend among critial care nutrition experts, which may be a reaction to the hypercaloric nutrition much in vogue during the 1970s and 1980s. Routine parenteral "hyperalimentation" was practiced, with patients frequently being fed up to 200% of their recommended energy requirements; contemporary recommendations called for 40-50 kcal/kg/day (Spanier et al, 1977) The expectation was that "in the depleted patient infusion of calories in excess of this amount results in a rebuilding of the body cell mass". 

Fortunately, we now know that this approach is stupid and dangerous. The pendulum has now swung towards underfeeding, with enthusiasts of hypocaloric nutrition placing an emphasis on using enteral nutrition for its non-nutritional benefits (eg. "trophic" feeding, discussed below).

Rationale for hypocaloric nutrition

In their answer to Question 23 from the first paper of 2017, the college offer a list of advantages in support of hypocaloric nutrition. This list can be expanded upon with references. 

In short:

We don't know how much nutrients the patients actually need. Ideal caloric targets for critically ill patients are unknown. Even calorimetry fails us (it tells us what they are using, but not what they require for optimal function). In short, without knowing what "eucaloric" feeding would look like, we can justify feeding at an intentionally reduced rate- it may actually be the required rate, for all we know.

There is a theoretical immunological advantage to hypocaloric nutrition. The college mention that "calorie restriction is associated with increased longevity in animal models", which is an interesting thing to mention. In this, the examiners have chosen to extrapolate to human critical care such experiments as Weindruch et al (1986), who demonstrated 30-40% longer lifespans for mice who were fed an incredibly poor diet (~ 65% calorie restricted). The unhappy rodents led an excruciatingly prolonged existance devoid of cake or bacon, generating no envy from the happily gluttonous control group (even though their lifespans averaged 53 months which according to the investigators "exceeds reported values for any mice of any strain").

The effect of 100% nutrition on muscle breakdown is unknown. That full nutritional support should prevent protein catabolism in critical illness is a widely believed fact, but we have little to support this. Streat et al (1987) fed their septic patients a luxuriously replete diet and found that they built more fatty tissue but lost muscle anyway. 

The hypercatabolic response to critical illness is adaptive, and working against it may be counterproductive. Disabling key autophagy genes leads to increased susceptibility to cancer and infectious diseases (Choi et al, 2013). The means of removing damaged organelles and digesting phagocytosed bacteria are activated by starvation and suppressed by nutrients (Van de Berge et al, 2012). In this manner, supplementation of 100% of goal needs may delay recovery from organ system failure and sepsis.

Feeding at goal rate may result in feed intolerance. This in turn leads to aspiration, use of prokinetics with dangerous side-effects, gastric distension, fluid overload and various other complications of enteral nutrition. Feeding below the goal rate should theoretically prevent or ameliorate these problems.

Permissive underfeeding

The definition of permissive underfeeding is somewhat nebulous. For example, that is what the PermiT trial (Arabi et al, 2015) called their 40-60% goal (i.e 40-60% of the expected daily nutritional requirements). Jeejeebhoy (2004) did not make any attempt to define the term in his review article. The systematic review by Owais et al (2010) reveals a massive variation of historical definitions, ranging though 13-14 kcal/kg/day, <20 kcal/kg/day, 1000 kcal/day,  or <33% of estimated requirement, or 5,000-10,000 kcal/week. Such unconservative proliferation of definitions gives rise to frustration and rage among critical care trainees, particularly where the definition accounts for 40% of a final exam question. The college offered the 40-60% goal from Arabi et al as their cut-off, which becomes the definitive mark-scoring answer to this definition.

Evidence for permissive underfeeding

In short, it is conflicting. If you separate the "tropic" trials, then there really is only one big study, which is the the PermiT trial by Arabi et al. The investigators randomised 894 patients (mostly intubated) to either receive 70-100% of their calculated requirements, or 40-60%. The groups ended up well separated (average 835 kcal vs. 1299) and this was maintained for 14 days. No difference in any of the primary outcome measures was found. A post-hoc analysis (Arabi et al, 2017) did not find any difference even among patients defined as being at a high nutritional risk. This has been viewed as evidence of safety. Provided you give 100% of the protein requirements, you can energy-restrict your ICU patients for two weeks with no adverse consequences.

Trophic feeding

In their answer to Question 23 from the first paper of 2017, the college defined trophic feeding as "feeding below the minimum required caloric intake, with the aim of maintaining gut integrity rather than meeting patient’s nutritional requirements". This closely resembles Sondheimer et al (2004), who were my source for the definition of trophic feeding as it is quoted:

"The generally accepted definition of trophic feeding is a small volume of balanced enteral nutrition insufficient for the patient's nutritional needs but producing some positive gastrointestinal or systemic benefit."

This article is actually an editor's perspective from the world of paediatric (specifically preterm neonatal) intensive care, where apparently exists an "almost religious" attachment to the concept of delivering a sub-nutritive volume of feeds. The definition also contains a certain daily caloric "target", i.e. one cannot call one's feeds "trophic" if one supplies more than 25% of the daily caloric goals in this way. Using the standard formula, that would mean keeping the total intake under 6.25 kcal/kg/day.

For adults, the definition of trophic feeding is largely based on the papers by Rice et al (discussed below), which used a rate of 10-20 cal/hr, up to a total of 500cal/day (which works out to be about 7 kcal/kg/day for a 70kg patient). The college give a range of 10-30ml/hr or 15-25% of calculated caloric intake.

Rationale for trophic feeding in critical illness

The expected benefits of this practice are:

• Improved feed tolerance (reduced gastric residual volumes)
• Maintenance of gastric and intestinal mucosal integrity
• Prevention of bacterial overgrowth and bacterial translocation
• Prevention of excessive protein catabolism (prevention of starvation)

Evidence for trophic feeding among critically ill adults

The large multicentre EDEN trial (Rice et al, 2012) followed an earlier single-centre 2011 study by the same authors into the territory of trophic feeding for ARDS patients. Unfortunately the investigators were roundly pilloried for undefeeding the patients with protein (0.6g/kg/day) and enrolling patients which were difficult to describe as "critically ill" with a straight face. The primary outcomes were completely unaffected by the trophic diet. All that can be said is that the lower volume of feeds (around 400cal/day) was better tolerated than full diet (i.e. the incidence of high gastric residual volumes was lower) which makes some sort of crude logical sense. This was hardly a great victory for people who expected some sort of positive effects from this strategy. However, it did suggest that there is probably little harm in the practice, for whatever that is worth. For five days, you can safely underfeed your ICU patients with energy input of around 400 calories. Additionally, is probably worth remembering that every 1ml of 1% propofol contains 1.1 calories of delicious soy-based lipid, and it is quite possible to supply a decent amount of energy that form (i.e. 15ml/hr for 24 hrs = 396 kcal/day).

Support from societies

ASPEN guidelines answered the question, "For which population of patients in the ICU setting is it appropriate to provide trophic EN over the first week of hospitalization?"  (McClave et al, 2016- p. 169). They answered using results from the ARDS-focused trials by Todd W. Rice et al (2012 and 2011). The exact phrase was "We recommend that either trophic or full nutrition by EN is appropriate" for patients with acute lung injury.