• Users Online: 57
  • Print this page
  • Email this page

Table of Contents
Year : 2019  |  Volume : 5  |  Issue : 1  |  Page : 12-16

Protein delivery in critical care

Consultant Critical Care, Department of Critical Care Medicine, Peerless Hospital, Kolkata, West Bengal, India

Date of Web Publication15-Nov-2019

Correspondence Address:
Dr. Rimita Dey
Peerless Hospital, Kolkata, West Bengal
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jrnm.jrnm_44_19

Get Permissions


Evidence suggests that improving the nutritional status has potential to improve the recovery of critically ill patients. Critically ill patients are at high risk of developing malnutrition due to various factors. Patients who develop sepsis, require prolonged ventilation and therefore are also at risk of developing neuromuscular paresis and have a high risk of mortality. Evidence suggests that improving the nutritional status has potential to improve the recovery of critically ill patients. This article deals with the importance of protein delivery in critically ill patients and how to monitor the adequacy of protein delivery.

Keywords: Critically ill, malnutrition, protein

How to cite this article:
Dey R. Protein delivery in critical care. J Renal Nutr Metab 2019;5:12-6

How to cite this URL:
Dey R. Protein delivery in critical care. J Renal Nutr Metab [serial online] 2019 [cited 2020 Sep 26];5:12-6. Available from: http://www.jrnm.in/text.asp?2019/5/1/12/271040

  Introduction Top

Critically ill patients are at high risk of developing malnutrition due to various factors. Patients who develop sepsis, require prolonged ventilation and therefore are also at risk of developing neuromuscular paresis. These factors further increase the chances of dying or developing complications that delay their recovery. The complications may cause prolonged stay in the intensive care unit, delayed liberation from mechanical ventilation, a higher risk of death, increased hospital cost, and impaired physical functioning and quality of life months after intensive care unit (ICU) admission.[1],[3] These observations speak to the importance of developing new strategies to aid in the recovery of the patients and reducing the complications. Evidence suggests that improving nutritional status has the potential to improve the recovery of critically ill patients.

In a study which analyzed 768 patients, 530 (69%) were calorie deficient and 696 (90%) were protein deficient during the whole ICU stay. The correlation coefficient of ICU length of stay was −0.443 and −0.465, and of days on mechanical ventilation of alive patients was −0.338 and −0.392 for calorie and protein deficit, respectively (P<0.001). Infectious complications were also significantly correlated (−0.346 for calorie deficit, −0.298 for proteins, P < 0.001). The mean calorie deficit of the patients discharged alive from the ICU was −2135.62 ± 1918.63, which was less compared with patients who expired (−2564.44 ± 2173.45 [P = 0.027]).[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19],[20],[21],[22],[23],[24],[25],[26],[27],[28],[29],[30],[31],[32],[33] This was also seen in-hospital outcome. The mean calorie deficit of patients discharged from hospital was −2039.36 ± 1888.82, which was less than the patients who expired after discharge from the ICU (−2603.99 ± 2126.53 [P = 0.002]) [Table 1] and [Table 2].[49]
Table 1: Correlation of complications with calorie and protein deficits

Click here to view
Table 2: Intensive care unit and hospital outcome related to cumulative calorie and protein deficits

Click here to view

  How Much Proteins are Required? Top

Statistical analysis of existing nutritional databases revealed a relationship between increased nutritional intake and improved clinical outcomes. It was shown that for additional 30 g/day of protein and 1000 cal/day of calories, critically ill patients have reduced infectious complications, shorter duration of mechanical ventilation and reduced mortality. So what are the requirements? After careful review of the published evidence, experts concluded that critically ill patients should receive up to 2.0–2.5 g/kg/day of proteins and receiving up to 80% of the protein that is prescribed is associated with optimal outcomes. The ASPEN guidelines suggest that the protein requirements are expected to be in the range of 1.2–2.0 g/kg of actual body weight per day and may likely be even higher in case of burns or polytrauma patients. Recent INS database shows much lower delivery of proteins in the current practice.

  Are Calories More Important Or The Proteins? Top

In another analysis using the same INS database, it is shown that proteins are more important than the calories. When they controlled for the calorie intake, they could still see a significant reduction in associated mortality when >80% of proteins are delivered compared with <80% (odds ratio [OR] for 60-day mortality, 0.68; 95% confidence interval [CI], 0.50–0.91). In contrast, when they controlled for protein administration, there is no incremental effect of increased caloric administration (OR, 0.89; 95% CI, 0.71–1.12).

  What Is The Current Practice? Top

Emerging evidence suggests that exogenous protein/amino acid supplementation has the potential to favorably affect protein balance and improves the recovery of critically ill patients. In the INS study, most of the protein delivery was from the enteral nutrition formulas (82.5%). An addition of 11.5% coming from parenteral amino acid sources a few from I/V amino acids alone (0.1%) [Figure 1]. There is good evidence now that exogenous amino acids have a positive impact on muscle mass.[48]
Figure 1: Positive response of protein delivery from the enteral nutrition formulas, parenteral amino acid sources and IV amino acids in intensive care unit (ICU)

Click here to view

  Concerns About Protein Administration Top

There are some concerns about increased mortality in some studies with increasing mortality with increasing nutritional status. Short-term mortality may not be the best outcome used to evaluate the effect of increased protein administration. Measures of muscle mass or function or patient-based performance measures (6 min walk test, measures of handgrip), if possible may be more sensitive to differential amounts of protein intake. Of note, Early versus Delayed Enteral Feeding to Treat People with Acute Lung Injury or Acute Respiratory Distress Syndrome compared goal feeding with trophic feeding and demonstrated no difference in short-term outcomes; however, better-fed patients had a trend toward improvements in long-term physical functional performance. Hence, the application of nutritional scoring systems to identify patients at risk, having a protocol for providing adequate nutritional intake, monitoring of the nutritional delivery, providing supplemental exogenous amino acids/proteins can be done to improve outcomes in the critically ill patients.

  How To Monitor Adequacy Of Protein Delivery? Top

Traditional serum protein markers (serum albumin, prealbumin, transferrin, and retinol-binding protein) are not markers of nutrition status in critical illness and are not recommended. Both mTOR and GCN2 regulate distinct gene, protein, and cell behavior responses that can refiect amino acid availability and might be readily measured in the clinical setting to identify patients who respond to protein therapy. Some investigators have reported the use of cleaved fraction of alpha-actin as a tool to assess protein degradation in humans.

Another tool used to refiect change in total body protein stores is the determination of nitrogen balance. Simply put, this is the difference between nitrogen intake and loss. The majority of nitrogen excretion occurs through the kidneys. Urinary nitrogen excretion typically increases during critical illness, and measuring 24-h urinary nitrogen, either as urea nitrogen (UUN) or total urinary nitrogen (TUN), has been used to determine protein needs. Each has its limitations; UUN seems to underestimate total nitrogen excretion (particularly in the most catabolic patients), and TUN is not widely available. Nevertheless, measuring urinary nitrogen can help us estimate an individual patient's catabolic state and perhaps guide protein administration. The presently recommended range of protein intake is broad, and measurement of urine nitrogen excretion could help us be more precise in our protein prescriptions.

  How to Increase Protein Delivery in Intensive Care Unit? Top

In the modern ICU medicine, the main cause of protein underdelivery in the ICU is related to the frequent interruptions to enteral feeding because of impending or current procedures.[34] To maximize enteral nutrition (EN) delivery, wefirst need to minimize the time patients are nil per oral with protocols that minimize these interruptions [Table 3] and [Table 4].[35] Then, using existing products and strategies, there are several methods by which practitioners can increase protein/amino administration in the ICU setting: using a high-protein enteral formula, adding protein supplements to the existing EN order, implementing novel enteral feeding protocols that include protein delivery enhancement strategies and/or volume-based feeding strategies,[34],[36],[37],[38],[39] and supplementation with parenteral amino acids alone or PN.[40]
Table 3: Protein adequacy in intensive care unit (ICU)

Click here to view
Table 4: Guideline for administering supplemental protein

Click here to view

  Protein Delivery In Special Populations Top

Patients with acute kidney injury and not on hemodialysis are a relative contraindication of higher protein supplementation. One needs to carefully ascertain the requirements, the catabolic stress, etc., before prescribing the supplementation proteins.

Another group would be refractory hepatic encephalopathy where benefits have to be weighed against the risks involved. Although sarcopenia in liver disease is a poor prognostic marker, and proteins have a great role in reversing sarcopenia and improving outcomes in liver disease, in refractory encephalopathy clinical judgment should be used before prescribing protein supplements.

  Conclusion Top

While it is difficult to be precise about how much protein critically ill patients require (and likely that amount varies across patient groups and within a patient over time), it is likely that “more” rather than “what” is currently, and suboptimally, being administered will result in improved outcomes for this patient population, especially for nutritionally “high-risk” patients. We encourage practitioners to achieve a minimum of 1.2–1.5 g/ kg/day and a maximum that approximates 2.0–2.5 g/kg/day. While future research clarifies the exact amount of protein required in various case mix groups of ICU patients or strengthens the available evidence that “more is better,” current quality improvement initiatives should work toward improving current practice, and hence current patients receive more protein. This is based on the notion that by waiting for confirmatory evidence or more precise information, current patients are possibly being harmed. Further research should also develop better tools to enable bedside practitioners to monitor optimal or adequate protein intake for individual patients. Finally, exploring the effect of combining protein intake with early mobility/exercise in the ICU setting has the greatest potential for improving the outcomes of survivors of critical illness and warrants further study.

Financial support and sponsorship


Confiicts of interest

There are no confiicts of interest.

  References Top

Fan E, Dowdy DW, Colantuoni E, Mendez-Tellez PA, Sevransky JE, Shanholtz C, et al. Physical complications in acute lung injury survivors: A two-year longitudinal prospective study. Crit Care Med 2014;42:849-59.  Back to cited text no. 1
De Jonghe B, Sharshar T, Lefaucheur JP, Authier FJ, Durand-Zaleski I, Boussarsar M, et al. Paresis acquired in the intensive care unit: A prospective multicenter study. JAMA 2002;288:2859-67.  Back to cited text no. 2
Hermans G, Van Mechelen H, Clerckx B, Vanhullebusch T, Mesotten D, Wilmer A, et al. Acute outcomes and 1-year mortality of intensive care unit-acquired weakness. A cohort study and propensity-matched analysis. Am J Respir Crit Care Med 2014;190:410-20.  Back to cited text no. 3
Hoffer LJ, Bistrian BR. Appropriate protein provision in critical illness: A systematic and narrative review. Am J Clin Nutr 2012;96:591-600.  Back to cited text no. 4
Heyland DK, Cahill N, Day AG. Optimal amount of calories for critically ill patients: Depends on how you slice the cake! Crit Care Med 2011;39:2619-26.  Back to cited text no. 5
Nicolo M, Heyland DK, Chittams J, Sammarco T, Compher C. Clinical outcomes related to protein delivery in a critically ill population: A multicenter, multinational observation study. JPEN J Parenter Enteral Nutr 2016;40:45-51.  Back to cited text no. 6
Alberda C, Gramlich L, Jones N, Jeejeebhoy K, Day AG, Dhaliwal R, et al. The relationship between nutritional intake and clinical outcomes in critically ill patients: Results of an international multicenter observational study. Intensive Care Med 2009;35:1728-37.  Back to cited text no. 7
Heyland DK, Stephens KE, Day AG, McClave SA. The success of enteral nutrition and ICU-acquired infections: A multicenter observational study. Clin Nutr 2011;30:148-55.  Back to cited text no. 8
Liebau F, Sundström M, van Loon LJ, Wernerman J, Rooyackers O. Short-term amino acid infusion improves protein balance in critically ill patients. Crit Care 2015;19:106.  Back to cited text no. 9
Hsieh LC, Chien SL, Huang MS, Tseng HF, Chang CK. Anti-infiammatory and anticatabolic effects of short-term beta-hydroxy-beta-methylbutyrate supplementation on chronic obstructive pulmonary disease patients in intensive care unit. Asia Pac J Clin Nutr 2006;15:544-50.  Back to cited text no. 10
Wei X, Day AG, Ouellette-Kuntz H, Heyland DK. The association between nutritional adequacy and long-term outcomes in critically ill patients requiring prolonged mechanical ventilation: A multicenter cohort study. Crit Care Med 2015;43:1569-79.  Back to cited text no. 11
Puthucheary ZA, Rawal J, McPhail M, Connolly B, Ratnayake G, Chan P, et al. Acute skeletal muscle wasting in critical illness. JAMA 2013;310:1591-600.  Back to cited text no. 12
Heyland D, Earthman C, Compher C. Acute muscle wasting among critically ill patients. JAMA 2014;311:621-2.  Back to cited text no. 13
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.  Back to cited text no. 14
Heyland DK, Wischmeyer PE. Does artificial nutrition improve outcome of critical illness? An alternative viewpoint! Crit Care 2013;17:324.  Back to cited text no. 15
Heyland DK, Stapleton RD, Mourtzakis M, Hough CL, Morris P, Deutz NE, et al. Combining nutrition and exercise to optimize survival and recovery from critical illness: Conceptual and methodological issues. Clin Nutr 2016;35:1196-206.  Back to cited text no. 16
Allingstrup MJ, Esmailzadeh N, Wilkens Knudsen A, Espersen K, Hartvig Jensen T, Wiis J, et al. Provision of protein and energy in relation to measured requirements in intensive care patients. Clin Nutr 2012;31:462-8.  Back to cited text no. 17
Weijs PJ, Looijaard WG, Beishuizen A, Girbes AR, Oudemans-van Straaten HM. Early high protein intake is associated with low mortality and energy overfeeding with high mortality in non-septic mechanically ventilated critically ill patients. Crit Care 2014;18:701.  Back to cited text no. 18
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.). JPEN J Parenter Enteral Nutr 2016;40:159-211.  Back to cited text no. 19
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.  Back to cited text no. 20
National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network, Rice TW, Wheeler AP, Thompson BT, Steingrub J, Hite RD, et al. Initial trophic vs. full enteral feeding in patients with acute lung injury: The EDEN randomized trial. JAMA 2012;307:795-803.  Back to cited text no. 21
Needham DM, Dinglas VD, Bienvenu OJ, Colantuoni E, Wozniak AW, Rice TW, et al. One year outcomes in patients with acute lung injury randomised to initial trophic or full enteral feeding: Prospective follow-up of EDEN randomised trial. BMJ 2013;346:f1532.  Back to cited text no. 22
Doig GS, Simpson F, Sweetman EA, Finfer SR, Cooper DJ, Heighes PT, et al. Early parenteral nutrition in critically ill patients with short-term relative contraindications to early enteral nutrition: A randomized controlled trial. JAMA 2013;309:2130-8.  Back to cited text no. 23
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.  Back to cited text no. 24
Kondrup J, Rasmussen HH, Hamberg O, Stanga Z. Ad Hoc ESPEN Working Group. Nutritional risk screening (NRS 2002): A new method based on an analysis of controlled clinical trials. Clin Nutr 2003;22:321-36.  Back to cited text no. 25
Jie B, Jiang ZM, Nolan MT, Zhu SN, Yu K, Kondrup J. Impact of preoperative nutritional support on clinical outcome in abdominal surgical patients at nutritional risk. Nutrition 2012;28:1022-7.  Back to cited text no. 26
Heyland DK, Dhaliwal R, Jiang X, Day AG. Identifying critically ill patients who benefit the most from nutrition therapy: The development and initial validation of a novel risk assessment tool. Crit Care 2011;15:R268.  Back to cited text no. 27
Rahman A, Hasan RM, Agarwala R, Martin C, Day AG, Heyland DK. Identifying critically-ill patients who will benefit most from nutritional therapy: Further validation of the “modified NUTRIC” nutritional risk assessment tool. Clin Nutr 2016;35:158-62.  Back to cited text no. 28
Compher C, Chittams J, Sammarco T, Nicolo M, Heyland DK. Greater protein and energy intake may be associated with improved mortality in higher risk critically ill patients: A multicenter, multinational observational study. Crit Care Med 2017;45:156-63.  Back to cited text no. 29
Mukhopadhyay A, Henry J, Ong V, Leong CS, Teh AL, van Dam RM, et al. Association of modified NUTRIC score with 28-day mortality in critically ill patients. Clin Nutr 2017;36:1143-8.  Back to cited text no. 30
Mendes R, Policarpo S, Fortuna P, Alves M, Virella D, Heyland DK, et al. Nutritional risk assessment and cultural validation of the modified NUTRIC score in critically ill patients-A multicenter prospective cohort study. J Crit Care 2017;37:249.  Back to cited text no. 31
Rosa M, Heyland DK, Fernandes D, Rabito EI, Oliveira ML, Marcadenti A, et al. Translation and adaptation of the NUTRIC score to identify critically ill patients who benefit the most from nutrition therapy. Clin Nutr ESPEN 2016;14:31-6.  Back to cited text no. 32
Arabi YM, Aldawood AS, Al-Dorzi HM, Tamim HM, Haddad SH, Jones G, et al. Permissive underfeeding or standard enteral feeding in high- and low-nutritional-risk critically ill adults. Post hoc analysis of the PermiT trial. Am J Respir Crit Care Med 2017;195:652-62.  Back to cited text no. 33
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.  Back to cited text no. 34
Parent BA, Mandell SP, Maier RV, Minei J, Sperry J, Moore EE, et al. Safety of minimizing preoperative starvation in critically ill and intubated trauma patients. J Trauma Acute Care Surg 2016;80:957-63.  Back to cited text no. 35
McCall M, Cahill N, Murch L, Sinuff T, Bray T, Tanguay T, et al. Lessons learned from implementing a novel feeding protocol: Results of a multicenter evaluation of educational strategies. Nutr Clin Pract 2014;29:510-7.  Back to cited text no. 36
McClave SA, Saad MA, Esterle M, Anderson M, Jotautas AE, Franklin GA, et al. Volume-based feeding in the critically ill patient. JPEN J Parenter Enteral Nutr 2015;39:707-12.  Back to cited text no. 37
Haskins IN, Baginsky M, Gamsky N, Sedghi K, Yi S, Amdur RL, et al. Volume-based enteral nutrition support regimen improves caloric delivery but may not affect clinical outcomes in critically ill patients. JPEN J Parenter Enteral Nutr 2017;41:607-11.  Back to cited text no. 38
Taylor B, Brody R, Denmark R, Southard R, Byham-Gray L. Improving enteral delivery through the adoption of the “Feed early enteral diet adequately for maximum effect (FEED ME)” protocol in a surgical trauma ICU: A quality improvement review. Nutr Clin Pract 2014;29:639-48.  Back to cited text no. 39
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.  Back to cited text no. 40
Abbot Nutrition. Vital High Protein; 2015. Available from: http://abbottnutrition.com/brands/products/vital-high-protein. [Last accessed on 2016 Oct 13].  Back to cited text no. 41
Nestle Health Science. Peptamen Intense High Protein. Nestle Health Science; 2016. Available from: https://www.nestlehealthscience.ca/en/brands/peptamen/peptamen-intense-hp. [Last accessed on 2016 Oct 13].  Back to cited text no. 42
McClave S, Bernard A, Huhmann M, Lowen CC, Ochoa J. Appropriateness of a very high protein, low carbohydrate formula in critically ill patients with obesity: A pilot study of design, safety and tolerance. JPEN J Parenter Enteral Nutr 2015;39:240.  Back to cited text no. 43
Hopkins B, Cohen SS, Irvin SR, Alberda C. Achieving protein targets in the ICU using a specialized high-protein enteral formula: A quality improvement project. Nutr Clin Pract 2019;1-10.  Back to cited text no. 44
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.  Back to cited text no. 45
Heyland DK, Dhaliwal R, Lemieux M, Wang M, Day AG. Implementing the PEP uP protocol in critical care units in Canada: Results of a multicenter, quality improvement study. JPEN J Parenter Enteral Nutr 2015;39:698-706.  Back to cited text no. 46
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.  Back to cited text no. 47
Heyland DK, Weijs PJ, Coss-Bu JA, Taylor B, Kristof AS, O'Keefe GE, et al. Protein delivery in the intensive care unit: Optimal or suboptimal? Nutr Clin Pract 2017;32:58S-71S.  Back to cited text no. 48
Dey R, Bhattacharyya M, Todi S. Impact of cumulative calorie and protein deficits in critically ill patients. Crit Care 2011;15 Suppl 1:P382.  Back to cited text no. 49


  [Figure 1]

  [Table 1], [Table 2], [Table 3], [Table 4]


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

  In this article
How Much Protein...
Are Calories Mor...
What Is The Curr...
Concerns About P...
How To Monitor A...
How to Increase ...
Protein Delivery...
Article Figures
Article Tables

 Article Access Statistics
    PDF Downloaded38    
    Comments [Add]    

Recommend this journal