March 7, 2019

Evaluating protein targets - a priority in critical care nutrition

What next for calorie intake in intensive care ?


What represents optimal calorie delivery in intensive care patients is controversial, with some studies suggesting increasing intake improves outcomes, whereas others suggest daily calorie intakes of around 1000 calories (termed ‘permissive underfeeding’) — or even as low as 400 calories — are not associated with adverse outcomes.

Currently, most ICU patients receive enteral feeding using formulation that has an energy content of approximately 1 kcal / ml, prescribed at a rate of approximately 1 ml / kg of body weight per hour (see here and here). However, due to factors such as gastrointestinal intolerance (defined as large gastric residual volumes, regurgitation, and vomiting) and fasting for procedures, less than 60% of recommended energy intake is usually delivered to patients (see here and here).

New research presented at the ESICM LIVES conference and published simultaneously in the New England Journal of Medicine shows that patients in intensive care units (ICU) do not survive any longer if they are given full daily recommended calorie requirements — meaning 50% more calories than they usually receive (which is recommended by current guidelines).

The research team was led by Professor Marianne Chapman, Royal Adelaide Hospital and University of Adelaide, and Professor Sandra Peake, The Queen Elizabeth Hospital and University of Adelaide, Adelaide, SA, Australia and colleagues.  They conducted a multi-centre, double-blind, randomised trial in 3957 mechanically ventilated adults across 46 Australian and New Zealand ICUs, comparing energy-dense (1.5 kcal/ml) (1971 patients) with routine (1.0 kcal/ml) enteral nutrition at a dose of 1 ml per kg ideal body weight per hour (1986 patients), commencing within 12 hours of the initiation of ICU nutrition support and continuing for up to 28 days.

Patients in the increased calorie group received a mean 1863 kcal/day vs. 1262 kcal/day in the 1.0 kcal/ml group (mean difference 601 kcal/day). The primary outcome of the study was all-cause mortality within 90 days.

By day 90, 523 of 1948 patients (26.8%) assigned to the 1.5 kcal/ml group had died, compared with 505 of 1966 patients (25.7%) in the 1.0 kcal/ml group, meaning no difference between the groups in terms of survival. Results were similar for seven pre-defined sub-groups.

Increased calorie delivery did not affect survival time, receipt of organ support, number of days alive and out of the ICU and hospital, or free of organ support, or the incidence of infective complications, or adverse events.

This is the first study in the ICU population to successfully deliver guideline-recommended calories by the enteral route. The authors concluded: “Increasing energy intake with the administration of energy-dense enteral nutrition did not affect survival in critically ill adults. Our findings do not support existing guidelines that recommend an energy intake energy of 25-30 kcal/kg/day, to match expenditure.”

The authors are now analysing data of functional outcomes in these patients at 6 months. They add: “It is possible that increased calorie delivery does not improve survival, but does improve recovery. We await this analysis with interest and thus cannot make comments about changes in recommendations until we have seen these results.”

In an Editorial published in Critical Care Resuscitation after the 2018 ESICM LIVES meeting, Professors Chapman and Peake and three co-authors asked “What should we target after TARGET?”

The editorial emphasises that the data from large-scale multi-centre randomised controlled trials suggest that early trophic feeding for 6 days (around 400 kcal/day), permissive underfeeding for 14 days (around 800 kcal/day),  standard care feeding (≈ 1300 kcal/ day: see here and here), and energy-dense enteral nutrition (around 1900 kcal/ day) result in similar patient outcomes. The authors say: “trials do not support a view that calorie intake is a major determinant of outcomes in heterogeneous groups of ICU patients or in several specific sub-groups.”

They note, however, that the findings apply to high income settings and that in-lower income countries, where malnutrition remains a problem, adequate calories in intensive care may be more important. They also stress that while calorie intake may not be vital early in ICU care, it might become more important later in care, during the recovery period.

Finally, they stress the importance of protein intake, concluding: “As loss of muscle mass and negative nitrogen balance are common in critically ill patients and are associated with morbidity and mortality, it is clear that evaluating protein targets is now a priority in the field of critical care nutrition.”


The study’s lead authors can be contacted via e-mail:

Professor Marianne Chapman (based at the Royal Adelaide Hospital and University of Adelaide, Adelaide, SA, Australia:

Co-lead author Professor Sandra Peake, The Queen Elizabeth Hospital and University of Adelaide, Adelaide. SA, Australia:


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