Protein in the ICU

December 15, 2022 5 min read

Learning objectives

By the end of this article, you should be able to:

  • Describe the role of protein in ICU patients
  • Understand the clinical evidence for protein in ICU patients
  • Explain how to manage the nutritional challenges in meeting protein targets

Patients in the Intensive Care Unit (ICU) setting have different nutritional needs compared to other hospitalised patients. Appropriate nutrition provision in the ICU is associated with improved patient outcomes, reduced length of hospital stay, decreased duration of dependence on mechanical ventilation and reduced infections.1 The clinical evidence for the nutritional needs of ICU patients is focused on preventing overfeeding and ensuring adequate protein provision.

In a healthy person, an inadequate supply of protein and energy results in protein energy malnutrition (PEM). In ICU patients, effects of PEM may be more pronounced than in healthy individuals and is associated with increased risk of 90-day mortality and 30-day unanticipated hospital readmission.2

Evidence supports the importance of proteins and amino acids in maintenance of body homeostasis; therefore, good nutrition must include adequate provision of protein. This is particularly important for patients in the ICU.3 Studies have shown sufficient provision of protein reduces mortality in adults4,5,6 and improves quality of life (QOL) at 3-month follow-up.6


Protein

Protein is a key nutrient for ICU patients as protein catabolism is increased in the critically ill patient and nutrition support cannot completely eliminate the subsequent skeletal muscle wasting.7 Malnutrition and muscle wasting generally occur during the ICU stay due to the effect of catabolic hormones, an imbalance between intake and requirements but also as a result of physical immobilisation.8

Unlike other macro and micronutrients, the human body does not “store” amino acids; therefore, there is no ready supply to access during metabolic stress.2 In ICU patients, the balance between catabolic and anabolic processes becomes skewed, as the accelerated rate of protein breakdown cannot be matched by the increased need for protein synthesis.2

Nutritional needs of ICU patients also change over time.9 Protein losses occur rapidly and early (acute phase = 0–5 days post-ICU admission) in the acute care patient; increasing as much as 4-fold in the first 24 hours in ICU.2 Losses also remain high during the chronic (>5 days post-ICU admission) and recovery phases (post-ICU discharge). Therefore, early and sustained provision of higher protein doses may be needed to ensure not only patient survival, but also recovery and post-ICU quality of life.2


Protein requirements

Based on international guidelines, recommended protein intakes in the ICU range between 1.2-2.2g protein/kg body weight/day. The most recent European Society for Clinical Nutrition and Metabolism (ESPEN) guidelines for clinical nutrition in the ICU recommends 1.3g/kg/day protein.8 This recommendation is based largely on observational studies as randomised controlled trials are less conclusive. An observational study by Weijs et al5 of 886 patients showed that ICU patients with 1.2-1.5 g/kg/day delivered protein had reduced 28-day mortality. Nicolo et al10 found in 2824 ICU patients an improvement in survival if patients received more than 80% of their protein target.

However, meeting protein requirements whilst preventing calorific over feeding can sometimes be a challenge depending on the availability of suitable enteral feed formulas. ESPEN also concluded that it is possible that similar to caloric targets, optimal protein targets change over time in the ICU and that a high protein intake is only beneficial if not associated with overfeeding.8


Protein and mortality in the ICU

Many the observational studies used to form the ESPEN recommendations used mortality as a primary outcome. At present there is no evidence from randomised control trials to demonstrate protein dose and mortality. A systematic review evaluating higher protein vs. low protein enteral formula in critically ill patients concluded that higher protein delivery may be associated with shorter ICU length of stay and higher protein delivery significantly attenuated muscle loss by about 3.4% per week.11 However, the same systematic review also concluded from some of the evaluated studies that higher protein delivery has no effect on mortality, infectious complications and hospital length of stay. There were, however, limitations in terms of study heterogeneity including protein dose.


Protein and functional outcomes in the ICU

There are no randomised control trials to date investigating protein dose and muscle related outcomes. However, a systematic review by Fetterplace et al12 identified one study that concluded that muscle mass loss, measured using quadricep muscle layer thickness, was attenuated with greater protein delivery (1.5g/kg/day) compared to the control group (1g/kg/day).

Studies evaluating the role of exercise alongside meeting protein requirements have shown some promising results. De Azevedo showed that a high-protein intake (1.48g/kg/day) and resistance exercise twice daily improved the physical quality of life and survival of critically ill patients.13


Nutritional challenges in meeting protein requirements

Feeding on ICU is often complex and interruptions to feeding, intolerance, and limited availability of higher-protein formulas can all be contributing factors to the under delivery of adequate nutrition. Overfeeding energy has been shown to increase carbon dioxide production, increase blood glucose and insulin requirements and increase triglycerides, all of which can delay recovery.14

Overfeeding of energy in the ICU is a common challenge due to the use of non-feed energy sources such as the lipid based sedative, propofol. Propofol provides 1.1kcal/ml and average caloric intake from propofol ranges from 60 kcals/day to 356 kcals/day.15

A recent review of current International Nutrition Survey data suggests that protein in critically ill patients is under prescribed and grossly under delivered. Heyland et al16 evaluated prescribed versus received and found only approximately 55% of patients (on approximately 0.7 g/kg/day) met prescribed protein requirements, with the majority of protein delivered coming from enteral nutrition formulas (82.5%).

There have been some debates about the provision of high amounts of proteins or amino acids during the early phase of critical illness. Based on recent literature and guidelines, gradual progression to caloric and protein targets during the initial phase of ICU stay is recommended. During the acute phase (day 1-3), progressive feeding should be initiated at 25% (day 1), 50% (day 2) and 75% (day 3), with the target of 1.3g/kg body weight/day achieved by day 4. This will help to prevent overfeeding which has been shown to have negative consequences on recovery and mortality.17


Nutritional solutions for meeting protein requirements in ICU

Standard enteral tube feeds that are classified as high energy (1.5kcal/ml) or more may help to meet energy requirements in the ICU. However, due to the need to avoid overfeeding in the acute phase of critical illness, under-feeding is a common problem, which then has a negative effect on protein intake. There are now several high protein enteral tube feeds available for use in this patient group. However, there can still be challenges with meeting energy and protein targets.

An alternative option could be to use a form of protein supplementation. Protein supplements can be used to meet protein requirements whilst avoiding overfeeding of energy. The provision of additional protein using a high protein supplement can also allow for greater flexibility in dosing.


Post-ICU recovery and nutrition

Post-ICU recovery nutrition is also important and there is currently limited evidence due to lack of studies evaluating nutritional intake in this period. A recent study published in 2022, PROSPECT-1,18 evaluated energy and protein intake, and reached targets, in the post-ICU period. The study showed that overall mean energy and protein adequacy for all nutritional groups was 82.3% (SD 18.3) and 83.1% (SD 19.8). They also found that patients needed up to six days to reach protein targets again. The study concluded that nutritional support in the post-ICU period is key to reach protein and energy targets.


Summary

Nutrition support for patients in the ICU setting is key to improved patient outcomes, reduced length of hospital stay, decreased duration of dependence on mechanical ventilation and reduced infection. It is important to recognise that protein needs should be met whilst also balancing energy requirements with risk of overfeeding. Protein supplementation can be used to supplement standard enteral formulas where a high energy source is being provided but the protein provision is inadequate.

References:
  1. Villet S et al. Negative impact of hypocaloric feeding and energy balance on clinical outcome in ICU patients. Clin Nutr. 2005 Aug;24(4):502-9. doi: 10.1016/j.clnu.2005.03.006. PMID: 15899538.
  2. De Waele E et al. Review of evolution and current status of protein requirements and provision in acute illness and critical care. Clin Nutr. 2021 May;40(5):2958-2973. doi: 10.1016/j.clnu.2020.12.032. Epub 2020 Dec 29. PMID: 33451860.
  3. Weijs P.J et al. Proteins and amino acids are fundamental to optimal nutrition support in critically ill patients.Crit Care. 2014; 18: 591
  4. Alberda, C et al. The relationship between nutritional intake and clinical outcomes in critically ill patients: results of an international multicenter observational study. Intensive Care Med 35, 1728–1737 (2009). https://doi.org/10.1007/s00134-009-1567-4.
  5. Weijs, P.J.M et al. (2012), Optimal Protein and Energy Nutrition Decreases Mortality in Mechanically Ventilated, Critically Ill Patients. Journal of Parenteral and Enteral Nutrition, 36: 60-68. https://doi.org/10.1177/0148607111415109
  6. Wei X et al. 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 Aug;43(8):1569-79. doi: 10.1097/CCM.0000000000001000. PMID: 25855901.
  7. Japur CC et al. Can an adequate energy intake be able to reverse the negative nitrogen balance in mechanically ventilated critically ill patients? J Crit Care. 2010 Sep;25(3):445-50. doi: 10.1016/j.jcrc.2009.05.009. Epub 2009 Aug 13. PMID: 19682853.
  8. Singer P et al. ESPEN guideline on clinical nutrition in the intensive care unit. Clin Nutr. 2019 Feb;38(1):48-79. doi: 10.1016/j.clnu.2018.08.037. Epub 2018 Sep 29. PMID: 30348463
  9. Wischmeyer, P,E. Are we creating survivors…or victims in critical care? Delivering targeted nutrition to improve outcomes. Current Opinion in Critical Care: August 2016 - Volume 22 - Issue 4 - p 279-284 doi: 10.1097/MCC.0000000000000332
  10. Nicolo, M., Heyland, D.K., Chittams, J., Sammarco, T. and Compher, C. (2016), Clinical Outcomes Related to Protein Delivery in a Critically Ill Population. Journal of Parenteral and Enteral Nutrition, 40: 45-51. https://doi.org/10.1177/0148607115583675
  11. Composition of Enteral Nutrition: High Protein vs. Low Protein [Internet]. Criticalcarenutrition.com. 2021 [cited July 2021]. Available from: www.criticalcarenutrition.com/docs/systematic _reviews_ 2018/4.2c%20High%20protein_2018.pdf. Accessed online September 2022.
  12. Fetterplace K et al. (2020) Systematic Review With Meta-Analysis of PatientCentered Outcomes, Comparing International Guideline Recommended Enteral Protein Delivery With Usual Care. J Parenter Enteral Nutr.; 44(4):610-620 3
  13. De Azevedo JRA et al. High-protein intake and early exercise in adult intensive care patients: a prospective, randomized controlled trial to evaluate the impact on functional outcomes. BMC Anesthesiol. 2021 Nov 13;21(1):283. doi: 10.1186/s12871-021-01492-6. PMID: 34773985; PMCID: PMC8590269.
  14. J. Leyland, R. Protein supplementation can help to meet requirements in critically ill patients on a mixed surgical and medical intensive care unit. Clinical Nutrition ESPEN,Volume 29,2019,Page 255
  15. Dickerson RN and Buckley CT. Impact of Propofol Sedation upon Caloric Overfeeding and Protein Inadequacy in Critically Ill Patients Receiving Nutrition Support. Pharmacy (Basel). 2021 Jul 1;9(3):121. doi: 10.3390/pharmacy9030121. PMID: 34287346; PMCID: PMC8293440.
  16. Heyland, D.K et al. (2017), Protein Delivery in the Intensive Care Unit: Optimal or Suboptimal?. Nutrition in Clinical Practice, 32: 58S-71S. https://doi.org/10.1177/0884533617691245
  17. Van Zanten, A.R.H et al. Nutrition therapy and critical illness: practical guidance for the ICU, post-ICU, and long-term convalescence phases. Crit Care 23, 368 (2019). https://doi.org/10.1186/s13054-019-2657-5
  18. Slingerland-Boot R et al. Prospective observational cohort study of reached protein and energy targets in general wards during the post-intensive care period: The PROSPECT-I study. Clin Nutr. 2022 Aug 9;41(10):2124-2134. doi: 10.1016/j.clnu.2022.07.031. Epub ahead of print. PMID: 36067584.