Skip to main content

How to achieve nutrition goals by actual nutrition guidelines

While more patients are surviving the hospitalization, ICU survivors frequently experience significant post-ICU morbidities including muscle weakness and impairments in physical functioning that can persist for years and results in significant healthcare-associated costs. One major factor contributing to this “post-ICU disability” is the loss of functional lean body mass, highlighting the importance of adequate nutrition support as an integral component in the treatment of critically ill patients. High protein intakes are expected to stimulate new protein synthesis, thereby preserving muscle mass [1]. Recent randomized trials demonstrated that providing increased total calories alone to ICU patients may not improve outcomes [2,3,4]. However, observational studies report that optimizing daily protein intake, rather than total caloric intake, decreases infections, mechanical ventilation duration, time to discharge, and mortality [5].

Enteral nutrient delivery is often impaired by gastrointestinal intolerance, fasting for diverse medical procedures, and lack of feeding protocols which belong to the major reasons why less than 60% of recommended protein intake is usually delivered to the general ICU patients [6]. Historically, the feeding protocol has largely been based on an hourly “rate-based” feeding (RBF) approach, while strategies about how to compensate these commonly occurring interruptions are lacking. Consequently, almost a decade ago, Heyland and colleagues introduced a novel enteral feeding protocol designed to overcome the main barriers to adequate delivery of enteral nutrition, the Enhanced Protein-Energy Provision via the Enteral Route Feeding Protocol (PEPuP protocol) [7]. The main component of this innovative protocol was a switch from RBF to volume-based feeds where the nutritional targets were expressed in a volume per day of a nutritional solution needed to achieve the protein per energy targets. The PEPuP protocol results in 12–15% increase in the amount of protein and calories received by the patient in the context of a cluster randomized multicenter trial [8].

With this background, Brierly-Hobson et al. have conducted a before-after study of implementing VBF in their “real-world” setting. They demonstrated that a comprehensive training of dieticians and immediate initiation of this feeding strategy represent key factors for success and that the implementation of this nutrition strategy is feasible and effectively increases the caloric and protein intake of critically ill patients. The magnitude of the nutritional improvements seen here is with 20% more protein delivered in the VBF-based group which is significantly higher than the rate-based group and comparably effective as the so-called PEPuP protocol [8]. Yet, although a significant increase of protein intake was achieved by using this protocol, not all their patients received optimal protein intake (> 80%) of the aimed target, which pose the question why the investigators did not consider the use of protein supplements. In a recent study, O’Keefe et al. demonstrated that the combined use of empiric EN protein supplement is safe, when used in combination with EN in critically ill patients, and reaches 2 g/kg/day of protein intake per day [9]. In fact, enteral protein supplementation is one of a number of possible ways which has previously been demonstrated to increase protein intake in critically ill patients [8]. Alternatively, the combined use of enteral and parenteral nutrition has previously been demonstrated to significantly increase the protein intake, whereas its clinical relevance still remains unknown [10]. However, the optimal timing of increasing protein intakes is still a matter of debate [1]. The provision of high protein intakes during the early phase of critical illness has been associated with detrimental effects [11], possibly related to an increased production of glucagon and oxidation of amino acids [12], or inhibition of autophagy [10]. Arguably, these latter findings were reported from cohorts of patients at low nutritional risk patients.

Indeed, nutrition support is thought to be of special relevance and as such recommended in patients with high severity of illness, with nutritional high risk, and with prolonged ICU stay [13]. In contrast to these findings, several RCTs demonstrated the safety of high-dose protein application [14] even in the early phase of acute critical illness [15].

One thing that everyone can agree on is that we need more RCTs in nutritionally high-risk patients to be sure of the optimal protein dose in this context. The low level of evidence argues for a formal comparison of the risk-to-benefit ratios of different amounts of protein intakes. The registry-based EFFORT trial is an example of such a study (NCT03160547). In this trial, nutritionally high-risk patients are randomized to usual protein dose (≤ 1.2 g/kg/day) or a higher protein dose (≥ 2.2 g/kg/day). In order to achieve the desired level of protein intakes, the systematic use of volume-based feeding protocols should be advocated as the standard of care, instead of RBF, in both groups, to increase the changes that patients in both groups achieve at least 80% of what has been prescribed. Figure 1 illustrates VBF as strategies to improve enteral nutrition delivery, when compared to RBF. Then, with additional enteral protein supplements or parenteral nutrition or intravenous amino acids, patients in the high-dose group will be able to reach the higher dose targets. We eagerly await the results of such informative trials to provide more information on the clinical impact of such a feeding strategy. In the meantime, to prevent ongoing under-delivery of protein, we recommend that VBF becomes the standard of care in clinical practice. Tools to assist in the implementation can be found on

Fig. 1
figure 1

Volume-based feeding as strategies to improve enteral nutrition delivery. ICU intensive care unit, VBF volume-based feeding, RBF rate-based feeding

Availability of data and materials

Not applicable


  1. Preiser J-C. High protein intake during the early phase of critical illness: yes or no? Crit Care. 2018;22:261.

    Article  Google Scholar 

  2. Casaer MP, Mesotten D, Hermans G, Wouters PJ, Schetz M, Meyfroidt G, et al. Early versus late parenteral nutrition in critically ill adults. N Engl J Med. 2011;365:506–17.

    Article  CAS  Google Scholar 

  3. Arabi YM, Aldawood AS, Haddad SH, Al-Dorzi HM, Tamim HM, Jones G, et al. Permissive underfeeding or standard enteral feeding in critically ill adults. N Engl J Med. 2015;372:2398–408.

    Article  CAS  Google Scholar 

  4. Heidegger CP, Berger MM, Graf S, Zingg W, Darmon P, Costanza MC, et al. Optimisation of energy provision with supplemental parenteral nutrition in critically ill patients: a randomised controlled clinical trial. Lancet. 2013;381:385–93.

    Article  Google Scholar 

  5. Heyland DK, Stapleton R, Compher C. Should we prescribe more protein to critically ill patients? Nutrients. 2018;10:462.

    Article  Google Scholar 

  6. Heyland DK, Dhaliwal R, Wang M, Day AG. The prevalence of iatrogenic underfeeding in the nutritionally “at-risk” critically ill patient: results of an international, multicenter, prospective study. Clin Nutr. 2015;34:659–66.

    Article  Google Scholar 

  7. Heyland DK, Cahill NE, Dhaliwal R, Wang M, Day AG, Alenzi A, et al. Enhanced protein-energy provision via the enteral route in critically ill patients: a single center feasibility trial of the PEP uP protocol. Crit Care. 2010;14:R78.

    Article  Google Scholar 

  8. Heyland DK, Murch L, Cahill N, McCall M, Muscedere J, Stelfox HT, et al. Enhanced protein-energy provision via the enteral route feeding protocol in critically ill patients: results of a cluster randomized trial. Crit Care Med. 2013;41:2743–53.

    Article  CAS  Google Scholar 

  9. O'Keefe GE, Shelton M, Qiu Q, Araujo-Lino JC. Increasing enteral protein intake in critically ill trauma and surgical patients. Nutr Clin Pract. 2019;40:159.

    Google Scholar 

  10. Wischmeyer PE, Hasselmann M, Kummerlen C, Kozar R, Kutsogiannis DJ, Karvellas CJ, et al. A randomized trial of supplemental parenteral nutrition in underweight and overweight critically ill patients: the TOP-UP pilot trial. Crit Care. 2017;21:142.

    Article  Google Scholar 

  11. Casaer MP, Wilmer A, Hermans G, Wouters PJ, Mesotten D, Van den Berghe G. Role of disease and macronutrient dose in the randomized controlled EPaNIC trial: a post hoc analysis. Am J Respir Crit Care Med. 2013;187:247–55.

    Article  Google Scholar 

  12. Thiessen SE, Derde S, Derese I, Dufour T, Vega CA, Langouche L, et al. Role of glucagon in catabolism and muscle wasting of critical illness and modulation by nutrition. Am J Respir Crit Care Med. 2017;196:1131–43.

    Article  CAS  Google Scholar 

  13. McClave SA, Taylor BE, Martindale RG, Warren MM, Johnson DR, Braunschweig C, 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 (A.S.P.E.N.). J Parenter Enteral Nutr. 2016;40:159–211.

    Article  CAS  Google Scholar 

  14. Fetterplace K, Deane AM, Tierney A, Beach LJ, Knight LD, Presneill J, et al. Targeted full energy and protein delivery in critically ill patients: a pilot randomized controlled trial (FEED trial). JPEN J Parenter Enteral Nutr. 2018;42:1252–62.

    Article  CAS  Google Scholar 

  15. Doig GS, Simpson F, Bellomo R, Heighes PT, Sweetman EA, Chesher D, et al. Intravenous amino acid therapy for kidney function in critically ill patients: a randomized controlled trial. Intensive Care Med. 2015;41:1197–208.

    Article  CAS  Google Scholar 

Download references


Not applicable


Not applicable

Author information

Authors and Affiliations



Both authors CS and DH contributed equally to all aspects of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Christian Stoppe.

Ethics declarations

Ethics approval and consent to participate

Not applicable

Consent for publication

Not applicable

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Stoppe, C., Preiser, JC. & Heyland, D. How to achieve nutrition goals by actual nutrition guidelines. Crit Care 23, 216 (2019).

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: