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 Table of Contents  
REVIEW ARTICLE
Year : 2019  |  Volume : 3  |  Issue : 1  |  Page : 58-60

Protein Requirement in Critically ill Patients


College of Medicine, King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center; Department of Intensive Care, King Abdulaziz Medical City, Riyadh, Saudi Arabia

Date of Web Publication30-May-2019

Correspondence Address:
Yaseen M Arabi
Department of Intensive Care, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, P. O. Box 22490, Riyadh 11426
Saudi Arabia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2543-1854.259480

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  Abstract 


Acute critical illness is associated with proteolysis which leads to immunosuppression, poor wound healing, intensive care unit (ICU)-acquired weakness, increased mortality, and delayed recovery. It has been suggested that exogenous protein should be supplemented in sufficient amounts to mitigate this protein loss. However, there is a continuing controversy regarding the optimal amount of protein that should be administered to critically ill patients and its impact on the outcomes. The current clinical practice guidelines recommend protein intake in the range of 1.2–2.5 g/kg per day. These guidelines are mostly based on observational studies and a few randomized controlled trials. In addition, small studies showed improvement in muscle mass or handgrip strength but with no effect on ICU mortality or length of stay due to small sample size and presence of confounders such as energy intake or due to heterogeneous population. On the other hand, there is some evidence suggesting that higher protein intake provided in the 1st week of illness may actually cause harm due to inhibition of autophagy or increased ureagenesis. Therefore, there is a need for a well-designed randomized multicenter clinical trial to evaluate the optimal protein requirement in different phases of critical illness, in different subgroups, and in nutritionally high-risk patients.

Keywords: Autophagy, calories, catabolism, critical illness, protein


How to cite this article:
Arabi YM, Sadat M. Protein Requirement in Critically ill Patients. Saudi Crit Care J 2019;3:58-60

How to cite this URL:
Arabi YM, Sadat M. Protein Requirement in Critically ill Patients. Saudi Crit Care J [serial online] 2019 [cited 2021 Mar 1];3:58-60. Available from: https://www.sccj-sa.org/text.asp?2019/3/1/58/259480




  Introduction Top


Acute critical illness is associated with breakdown of muscle proteins or proteolysis. The resulting amino acids serve as substrates for the rapid protein synthesis occurring in the liver, splanchnic organs, bone marrow, and immunologically active tissues as part of the body reaction to the injury for tissue repair and inflammatory and immune response.[1] However, excessive proteolysis has been associated with immunosuppression, poor wound healing, intensive care unit (ICU)-acquired weakness, increased mortality, and delayed recovery. It has been suggested that exogenous protein should be supplemented in sufficient amounts to mitigate protein loss. It is well established that this breakdown is more pronounced in the early phase of illness which then subsides gradually during recovery.[2] Observational studies have demonstrated that the achievement of >90% of target protein intake in the early phase of illness was associated with improved ICU outcomes in mechanically ventilated critically ill patients.[3],[4] On the other hand, increased administration of exogenous protein may have adverse consequences. In critically ill patients, it has been associated with increased urea production and increased excretion of nitrogen in the urine.[5],[6] Furthermore, amino acid infusion may increase amino acid catabolism in the liver, mediated by increased glucagon, without preventing muscle wasting.[7] There is some evidence suggesting that higher protein intake may actually cause harm through inhibition of autophagy and increased ureagenesis.[8],[9] The controversy regarding the amount of protein required is further confounded by the heterogeneity among critically ill patients. Therefore, the impact of protein intake on outcomes in critically ill patients remains unclear and is considered a high research priority.[10]


  Increased Protein Intake Is Beneficial Top


The current clinical practice guidelines[11],[12] based on observational studies recommend protein intake in the range of 1.2–2.5 g/kg per day.[3],[13],[14] There are only small randomized controlled trials supporting this recommendation. A single-blinded randomized trial concluded that critically ill patients fed with a high-protein diet enriched with arginine, fiber, and antioxidants had a significantly lower catheter-related sepsis rate than patients fed a standard protein diet. There were no differences in mortality or ICU and hospital length of stay.[15] Ferrie et al. demonstrated a significant improvement in muscle mass and a trend toward increased handgrip strength in the group that received higher protein, but differences in protein received between the two groups were small (1.1 vs. 0.9 g/kg/day).[16]


  Increased Protein Intake Does not Make a Difference Top


Some studies showed no difference in the clinical outcomes with the increased protein dose.[17],[18],[19] The lack of benefit observed in some studies may be related to small sample size, presence of confounders such as increased energy with the high-protein group like in the trial by Rugeles et al.,[18] or heterogeneous patient population with varying nutritional risk, who may not respond similarly to the different doses of the protein. The Permissive Underfeeding versus Target Enteral Feeding in Adult Critically Ill Patients trial showed no difference in the primary outcome of mortality between the restricted caloric intake compared with standard feeding while targeting the full recommended amount of protein in both groups.[20] A subsequent secondary analysis using propensity score adjustment demonstrated no difference in outcomes among patients who received lower (0.6 ± 0.2 g/kg/day) versus higher protein intake (1.0 ± 0.2 g/kg/day) although the difference in protein between the two groups was moderate.[6]


  Reduced Protein Intake Is Beneficial Top


There is evidence suggesting that higher protein intake may cause harm through inhibition of autophagy and increased ureagenesis.[9],[21] There are studies suggesting that higher protein delivery in the 1st week of illness may be associated with greater muscle wasting[22] and delayed delivery.[5] A post hoc analysis of a small randomized trial of aggressive nutritional interventions (Intensive Nutrition in Acute Lung Injury Trial) where patients received approximately 80 g of protein per day compared to a usual care group which received around 60 g/day demonstrated that the amount of protein received in the 1st week was associated with a significant increased risk of death, whereas protein provided after the 1st week seemed protective.[23] Likewise, the post hoc analysis of the Early Parenteral Nutrition Completing Enteral Nutrition in Adult Critically Ill Patients trial showed that increased protein intake in the 1st week was associated with delayed recovery.[5]

Therefore, the optimal amount of protein intake and its association with the phases of illness in critically ill patients remains largely unclear and is considered a high priority for conducting a well-designed randomized clinical trial to settle the discrepancy between the results of reported studies.


  Questions Which Will Need to Be Answered Top


  1. Optimal protein requirement in patients with critical illness
  2. Protein requirement for critically ill patient subgroups such as trauma, burns, renal failure, liver disease, or older patients
  3. Specific protein requirement for patients in different phases of their critical illness, early or late
  4. Protein requirement in nutritionally high-risk patients.



  below Is the Summary of Some of the Ongoing Randomized Controlled Trials Addressing Protein Intake Top


  1. Nutrition and Exercise in Critical Illness: A Randomized Trial of Combined Cycle Ergometry and Amino Acids in the ICU (NEXIS) Trial[24] is funded by the National Institute of Health and evaluates the effect of early bedside cycling and intravenous amino acids to a maximum of 2.5 g/kg/day on the physical recovery of the ICU patients. The physical recovery is evaluated by a 6-min walk test. Other outcomes include muscle mass, muscle strength, functional capacity, and quality of life. The sample size is 142 patients and the trial is currently ongoing
  2. The Effect of Higher Protein Dosing in Critically Ill Patients (EFFORT) Trial[25] is a large, multicenter, pragmatic, registry-based, randomized clinical trial of 4000 nutritionally high-risk critically ill patients who are randomly allocated to a higher dose of protein (≥2.2 g/kg/day) or usual care (≤1.2 g/kg/day). The primary outcome for this trial is 60-day mortality. The secondary outcomes include time-to-discharge-alive, nutritional adequacy, hospital mortality, readmission to ICU and hospital, and duration of mechanical ventilation, ICU stay, and hospital stay. The trial is currently ongoing
  3. Replacing Protein via Enteral Nutrition in a Stepwise Approach in Critically Ill Patients (REPLENISH) Trial[26] is a randomized trial that compares high protein (1.8–2.2 g of protein/kg/day) to low protein (0.8–1.0 g of protein/kg/day) intake in adult, medical-surgical critically ill patients. Patients receive moderate amount of protein and energy till day 5 and then they are randomized on day 5. The primary outcome is 90-day mortality. A feasibility pilot study with a sample size of 40 patients is ongoing at three sites in Saudi Arabia
  4. TARGET-Protein Trial[27] is a prospective, blinded, parallel group, randomized feasibility trial which will enroll patients from ICUs participating in TARGET-The Augmented versus Routine approach to Giving Energy Trial.[28] Patients will receive two liquid nutrient formulae in a blinded fashion with different amounts of protein but similar calories.



  Conclusion Top


The upcoming trials will likely help further understand the optimal protein requirement in different phases of critical illness, in different subgroups, and in nutritionally high-risk patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Radrizzani D, Iapichino G, Cambisano M, Bonetti G, Ronzoni G, Colombo A. Peripheral, visceral and body nitrogen balance of catabolic patients, without and with parenteral nutrition. Intensive Care Med 1988;14:212-6.  Back to cited text no. 1
    
2.
Bendavid I, Zusman O, Kagan I, Theilla M, Cohen J, Singer P. Early administration of protein in critically ill patients: A Retrospective cohort study. Nutrients 2019;11. pii: E106.  Back to cited text no. 2
    
3.
Weijs PJ, Stapel SN, de Groot SD, Driessen RH, de Jong E, Girbes AR, et al. Optimal protein and energy nutrition decreases mortality in mechanically ventilated, critically ill patients: A prospective observational cohort study. JPEN J Parenter Enteral Nutr 2012;36:60-8.  Back to cited text no. 3
    
4.
Song JH, Lee HS, Kim SY, Kim EY, Jung JY, Kang YA, et al. The influence of protein provision in the early phase of intensive care on clinical outcomes for critically ill patients on mechanical ventilation. Asia Pac J Clin Nutr 2017;26:234-40.  Back to cited text no. 4
    
5.
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.  Back to cited text no. 5
    
6.
Arabi YM, Al-Dorzi HM, Mehta S, Tamim HM, Haddad SH, Jones G, et al. Association of protein intake with the outcomes of critically ill patients: A post hoc analysis of the PermiT trial. Am J Clin Nutr 2018;108:988-96.  Back to cited text no. 6
    
7.
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.  Back to cited text no. 7
    
8.
Henagan TM, Laeger T, Navard AM, Albarado D, Noland RC, Stadler K, et al. Hepatic autophagy contributes to the metabolic response to dietary protein restriction. Metabolism 2016;65:805-15.  Back to cited text no. 8
    
9.
Derde S, Vanhorebeek I, Güiza F, Derese I, Gunst J, Fahrenkrog B, et al. Early parenteral nutrition evokes a phenotype of autophagy deficiency in liver and skeletal muscle of critically ill rabbits. Endocrinology 2012;153:2267-76.  Back to cited text no. 9
    
10.
Arabi YM, Casaer MP, Chapman M, Heyland DK, Ichai C, Marik PE, et al. The intensive care medicine research agenda in nutrition and metabolism. Intensive Care Med 2017;43:1239-56.  Back to cited text no. 10
    
11.
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. 11
    
12.
Taylor BE, McClave SA, 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.). Crit Care Med 2016;44:390-438.  Back to cited text no. 12
    
13.
Ishibashi N, Plank LD, Sando K, Hill GL. Optimal protein requirements during the first 2 weeks after the onset of critical illness. Crit Care Med 1998;26:1529-35.  Back to cited text no. 13
    
14.
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. 14
    
15.
Caparrós T, Lopez J, Grau T. Early enteral nutrition in critically ill patients with a high-protein diet enriched with arginine, fiber, and antioxidants compared with a standard high-protein diet. The effect on nosocomial infections and outcome. JPEN J Parenter Enteral Nutr 2001;25:299-308.  Back to cited text no. 15
    
16.
Ferrie S, Allman-Farinelli M, Daley M, Smith K. Protein requirements in the critically ill: A randomized controlled trial using parenteral nutrition. JPEN J Parenter Enteral Nutr 2016;40:795-805.  Back to cited text no. 16
    
17.
Clifton GL, Robertson CS, Contant CF. Enteral hyperalimentation in head injury. J Neurosurg 1985;62:186-93.  Back to cited text no. 17
    
18.
Rugeles SJ, Rueda JD, Díaz CE, Rosselli D. Hyperproteic hypocaloric enteral nutrition in the critically ill patient: A randomized controlled clinical trial. Indian J Crit Care Med 2013;17:343-9.  Back to cited text no. 18
[PUBMED]  [Full text]  
19.
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. 19
    
20.
Arabi YM, Aldawood AS, Solaiman O. Permissive underfeeding or standard enteral feeding in critical illness. N Engl J Med 2015;373:1175-6.  Back to cited text no. 20
    
21.
Hermans G, Casaer MP, Clerckx B, Güiza F, Vanhullebusch T, Derde S, et al. Effect of tolerating macronutrient deficit on the development of intensive-care unit acquired weakness: A subanalysis of the EPaNIC trial. Lancet Respir Med 2013;1:621-9.  Back to cited text no. 21
    
22.
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. 22
    
23.
Braunschweig CL, Freels S, Sheean PM, Peterson SJ, Perez SG, McKeever L, et al. Role of timing and dose of energy received in patients with acute lung injury on mortality in the Intensive NuTrition in ACute lung injury Trial (INTACT): A post hoc analysis. Am J Clin Nutr 2017;105:411-6.  Back to cited text no. 23
    
24.
Nutrition and Exercise in Critical Illness (NEXIS). Available from: https://www.clinicaltrials.gov/ct2/show/NCT03021902. [Last accessed on 2018 Sep 26].  Back to cited text no. 24
    
25.
Heyland DK, Patel J, Bear D, Sacks G, Nixdorf H, Dolan J, et al. The effect of higher protein dosing in critically ill patients: A multicenter registry-based randomized trial: The EFFORT trial. JPEN J Parenter Enteral Nutr 2019;43:326-34.  Back to cited text no. 25
    
26.
Replacing Protein Via Enteral Nutrition in a Stepwise Approach in Critically Ill Patients (Replenish). Available from: https://www.clinicaltrials.gov/ct2/show/NCT03480555. [Last accessed on 2018 Sep 26].  Back to cited text no. 26
    
27.
TARGET Protein Feasibility Trial. Available from: https://www.anzics.com.au/current-active-endorsed-research/target-protein-feasibility-trial/. [Last accessed on 2019 Mar 17].  Back to cited text no. 27
    
28.
TARGET Investigators on behalf of the Australian and New Zealand Intensive Care Society Clinical Trials Group. Study protocol for the augmented versus routine approach to giving energy trial (TARGET). Crit Care Resusc 2018;20:6-14.  Back to cited text no. 28
    




 

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Introduction
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