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Table of Contents
Year : 2022  |  Volume : 6  |  Issue : 2  |  Page : 85-90

Effects of Parenteral Protein Concentrations in Critically Ill Patients in ICU: A Comparative Study

Department of Anesthesiology and Intensive Care, Faculty of Medicine, Minia University, El-Minya, Egypt

Date of Submission16-Feb-2022
Date of Decision06-Mar-2022
Date of Acceptance11-Mar-2022
Date of Web Publication09-May-2022

Correspondence Address:
Karim Naser Hasan
Department of Anesthesiology and Intensive Care, Faculty of Medicine, Minia University, El-Minya
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/bjoa.bjoa_57_22

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Background: Parenteral protein supplements can prevent deterioration of acute critical illness during admission at intensive care unit (ICU). This study aimed to evaluate the effect of parenteral proteins on ICU outcome and to compare the effect of two different protein concentrations on handgrip strength in critically ill patients. Materials and Methods: This prospective comparative study included 60 acute critically ill patients who had parenteral nutrition during their ICU stay. The patients were divided into two groups: a standard protein group who received protein concentration of 1 g/kg/day (group A) and a high-protein group who received protein concentration of 2 g/kg/day (group B). The nutrition was delivered through a central line and the separate bottles technique. Results: Nitrogen balance was more negative in group B compared to group A within the first 3 days. The handgrip strength on day 7 was significantly higher in group B than group A. The forearm thickness, quadriceps muscle thickness, and overall muscle thickness were significantly higher in group B on day 7. The durations of mechanical ventilation, ICU stay, and total hospital stay were not significantly different between both groups. The protein dose was not significantly associated with the overall 2-month mortality. Conclusion: High parenteral protein intake (2 g/kg/day) associated with better handgrip strength and significant improvement of muscle thickness at the end of the 1st week of follow-up. Studies with larger sample size and longer durations of follow-up are recommended.

Keywords: Critical care, critical illness, malnutrition, parenteral nutrition, proteins

How to cite this article:
Youssef IA, Hasan KN, Mohmed AH. Effects of Parenteral Protein Concentrations in Critically Ill Patients in ICU: A Comparative Study. Bali J Anaesthesiol 2022;6:85-90

How to cite this URL:
Youssef IA, Hasan KN, Mohmed AH. Effects of Parenteral Protein Concentrations in Critically Ill Patients in ICU: A Comparative Study. Bali J Anaesthesiol [serial online] 2022 [cited 2022 Aug 18];6:85-90. Available from: https://www.bjoaonline.com/text.asp?2022/6/2/85/344888

  Introduction Top

Malnutrition with depletion of essential micronutrients and erosion of body mass is very common in critically ill patients, with 20 to 40% of those patients showing evidence of protein-energy malnutrition.[1] The major goal of nutritional support is to provide patients with their daily nutritional requirements. So, we should know how to determine the nutrient and energy needs of each patient in the intensive care unit (ICU).[2]

Adequate nutrition is essential for critically ill patients as they have high-energy expenditure, which mandates high-energy nutrition; also they lose muscle as a result of an inability to maintain the rates of protein synthesis above those of protein breakdown, besides the effects of procatabolic hormones and cytokines.[3] Feeding of critically ill patients should be started early with initiation of nutritional therapy within 48 h of either hospital admission or surgery.[4] Guidelines recommend that when enteral nutrition (EN) is not possible, parenteral nutrition (PN) should be initiated within 3 days.[5] The clinical practice guidelines suggest that PN should be initiated without delay, especially for patients who have protein-energy malnutrition at the time of admission to the ICU.[1]

Protein-energy deficit is frequently observed with using EN alone and is associated with increased morbidity and mortality. Thus, avoiding nutritional deficiencies is a fundamental objective of nutritional therapy in ICU. Because EN is often difficult to fully optimize in the first 3 days of ICU admission, using EN with PN could allow a better coverage to achieve the energy target and decrease the protein-energy deficit.[6] PN should start as soon as possible to prevent the rapid deterioration of acute critical illness. It is hypothesized that large dose of protein supplements, especially during the early period, is beneficial in these cases. Therefore, this study aimed to evaluate the effect of parenteral proteins on outcome during ICU admission of critically ill patients and to compare the effect of two different protein concentrations on handgrip strength in these patients.

  Materials and Methods Top

This prospective comparative study was conducted on 60 abdominal surgery/trauma ICU patients who had a contraindication or intolerance to EN and were fed parenterally within 24–48 h from admission at our surgical ICU during the period from January 2020 to March 2021. Patients were divided according to the protein delivery into two groups: group A patients received parenteral proteins in a dose of 1 g/kg/day and group B patients received parenteral proteins in a dose of 2 g/kg/day. Caloric requirements were fixed at 25–30 kcal/kg/day for both groups. The age of the patients ranged from 18 to 70 years. Exclusion criteria were any pregnant female and any hepatic or renal patient. Patients were also excluded if they were younger than 18 years (as growth alters protein requirement). The study was approved by institutional ethical committee (308:10/2019), and a written informed consent was obtained from the patient, or if not possible, the next of kin provided consent. The study was also registered at ClinicalTrials.gov with an identifier number NCT04961866 dated on July 14, 2020.

All PN was delivered through a central venous access device and using the separate bottles technique. Because of the lack of a compounding unit and commercial bags in our hospital, the two solutions were packed identically by the hospital’s independent pharmacist and labeled clearly. The protein content was given as 10%; the rest of the energy requirement was divided between carbohydrates (glucose 25%) and lipids (Soya oil (6%), Medium chain triglycerides (6%), Olive oil (5%), and Fish oil (3%) [SMOF 20%]) in a ratio of 60:40 targeting 30 kcal/kg.

Mid-upper arm circumference was measured on the right arm to the nearest 1 mm at a point midway between the superior and lateral projection of the acromion process of the scapula and the proximal and lateral border of the head of the radius. Diagnostic two-dimensional ultrasonography was used to measure muscle thickness of the flexor compartment of the mid-upper arm perpendicularly from the bone to the superficial fat muscle. Ultrasound was used to measure the thickness of bicep muscles, forearm muscles, and thigh muscles. Triplicate measures were obtained, and the mean of the three measurements was used. The total of the mean values for the three measurement sites was recorded on each of days 0, 3, and 7.

Bedside Subjective Global Assessment (SGA) method was used to classify grade of malnutrition and identify those who would benefit from nutrition care using a physical examination as well as data obtained from the patient or family about previous weight loss, changes in dietary intake, nutrition impact symptoms such as diarrhea or poor appetite, and physical function. Acceptably nourished patients were classified as SGA “A,” severely malnourished patients were classified as SGA “C,” and patients who were mild to moderately malnourished or suspected of malnutrition were classified as SGA “B.” The Sequential Organ Failure Assessment (SOFA) score was used for calculation of both the number and the severity of organ dysfunction in six organ systems (respiratory, coagulation, liver, cardiovascular, renal, and neurologic). The second version of the Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE II) score was used to determine the level and degree of diagnostic and therapeutic intervention.

Handgrip strength was measured using the Camry electronic handgrip dynamometer [Figure 1] at day 3, day 7, and discharge. It is a measure of the maximum static force that a hand can squeeze using the device. It was used on the right arm with the patient lying in bed with head and shoulders raised to 30° and elbows supported by the bed. The shoulder was adducted and neutrally rotated, and the forearm and wrist were lying on the bed in a neutral position. Measures were performed at least 3 h after waking or stopping sedation. In cases of ventilated patients, it was performed after extubation and weaning from the ventilator and after stopping of sedation and muscle relaxant for reliable results. Urinary urea nitrogen was calculated and a value of 4 g nitrogen was added to allow for nonurinary nitrogen losses as well as urinary nitrogen sources other than urea. Nitrogen balance was calculated by subtracting these nitrogen losses from nitrogen intake (total of all sources) at day 3 and day 7.
Figure 1: The Camry electronic handgrip dynamometer used to measure the maximum static force of the hand

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The statistical analysis was carried out using Statistical Package for the Social Sciences software version 23.0. Descriptive statistical measures were number and percentage for categorical data and median with interquartile range for quantitative data. Parametric t-test or nonparametric Mann–Whitney test were used to compare quantitative data in accordance to the results of Shapiro–Wilk test of normality, whereas the chi-squared test or Fisher’s exact test was used to compare categorical data. P-value was considered significant if less than .05.

  Results Top

There were no statistically significant differences in baseline clinical and nutritional characteristics between both groups [Table 1]. The APACHE II and SOFA scores were slightly lower in group A than in group B with no statistically significant difference. The most common reason for PN among both groups was abdominal trauma.
Table 1: Baseline clinical and nutritional characteristics of the studied groups

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Most of the patients in both groups were acceptably nourished. Nitrogen balance on 3rd and 7th day is presented in [Table 2]. At study day 3, median nitrogen balance in group B was significantly higher than that in group A (−4.9 vs. −0.5, P < .001), whereas on day 7, there was no statistically significant difference in median nitrogen balance between the two groups. Mean handgrip strength [Figure 2] increased significantly on day 7 in group B (15.9 ± 3 vs. 19.2 ± 4.6, P = .002), whereas on day 3 and on discharge, the values were comparable. On study day 3, there was no statistically significant difference in all measurements of muscle thickness between both groups [Figure 3]. On study day 7, mean muscle thickness of forearm, thigh, and sum of muscle sites in group A was significantly lower than that in group B (2.4 ± 0.6 vs. 3.3 ± 0.7, 5.9 ± 0.1 vs. 6.7 ± 0.3, 7.9 ± 0.8 vs. 8.8 ± 0.7, respectively, P < .001).
Table 2: Nitrogen balance on the 3rd and 7th day in the studied groups

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Figure 2: Mean handgrip strength across time in both groups on day 3, day 7, and discharge

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Figure 3: Differences between both groups in mean of (a) biceps thickness, (b) forearm thickness, (c) thigh thickness, and (d) sum of muscle thickness at 3rd and 7th days of ICU stay

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Hospital durations and outcome of both groups are presented in [Table 3]. Mechanical ventilation was required in 16.7% of group A compared to 13.3% of group B. There was no statistically significant difference between both groups in regard to duration of mechanical ventilation, length of ICU stays, and length of total hospital stay. Two-month mortality was 10% in group A compared to 6.7% in group B with no statistically significant difference.
Table 3: Hospital duration and outcome of the studied groups

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  Discussion Top

Malnutrition is a global concern among patients admitted to ICU, especially in developing countries. About 20% of ICU patients suffer from malnutrition, and this prevalence reached 64% among developing countries.[7] If the required daily caloric intake is not achieved, unfavorable consequences would happen such as increased length of stay, increased progression of the disease, and mechanical ventilation.[8] Critically ill patients admitted to ICU need additional requirements of caloric intake to compensate for their protein loss. So they need to be fed by external sources to improve their prognosis and decrease the length of stay. PN is the only source of nutrition for critically ill patients as they are unable to feed themselves.[9]

To assess the effectiveness of PN, nitrogen balance is measured as a tool for early monitoring of dose sufficiency among patients.[10] It is known that most patients in ICU are prone to protein catabolism and this makes a high proportion of them on a negative nitrogen balance. Kim et al. reported that 80% of patients admitted to ICU had negative nitrogen balance, improvement of malnutrition, and reduction of negative nitrogen balance associated with significantly better functional outcomes and less duration of hospital stay.[11] In our study, we managed critically ill patients to achieve a less negative nitrogen balance. High-protein intake associated with significantly lower nitrogen balance on day 3, whereas this difference was insignificant on day 7.

Handgrip strength is considered an early predictor for acquired muscle weakness. It is considered a noninvasive accurate method for determining the nutrition adequacy of patients in ICU.[12] Flood et al. found that handgrip strength was significantly low among patients with severe malnutrition status when compared with those with good nutritional status (14 ± 7.6 vs. 27.2 ± 11.7, respectively).[13] Moreover, Ali et al. reported that handgrip strength could be a precise indicator for acquired weakness among ICU patients.[14] In our study, patients who received high protein doses had higher handgrip strength than patients with low protein doses on day 7 (15.9 ± 3 vs. 19.2 ± 4.6).

Additionally, we used ultrasonographic measurement of muscle mass as an objective method for nutritional assessment. It is a portable non-invasive method that can be used to assess the nutritional status in immobilized and unconscious patients for a long time.[15] Thigh muscle thickness can be measured through ultrasonography. Any changes in the circumference of thigh muscle would reflect the nutritional status of patients. In our study, we found that thigh muscle thickness was higher among those with higher protein intake compared to those with lower ones at day 7; however, this difference was slightly apparent on day 3. Our findings of more handgrip strength and higher thigh muscle thickness among patients with high-dose protein are consistent with the reported results by other investigators.[16]

We also found that patients with high-protein intake had shorter durations of ICU stay compared to patients with low doses, but with statistically insignificant difference. This finding is in consistence with the recently reported findings by Dresen et al.[17] Immobilization or stay in bed is considered as a form of treatment in critically ill patients, so that the length of stay is considered as a principal parameter for prognosis of those patients. Reduced duration of ICU stay can minimize the complications for critically ill patients, e.g., it decreases the delirium of those patients by 2 days.[18] Additionally, we found that low-protein dose was associated with statistically insignificant higher mortality rate among critically ill patients compared to higher doses (10% vs. 6.7%, respectively). This was consistent with the findings by Arabi et al. who reported insignificant difference in mortality between low- and high-protein intake groups.[19] Moreover, Looijaard et al. found that early high-protein intake is associated with lower mortality in critically ill patients who had early high-protein intake, especially those with low skeletal muscle area and density on admission.[20]

  Conclusion Top

Critical illness is considered a life-threatening condition that alters muscle metabolism. High-protein intake was not associated with a decrease in ventilator days, ICU length of stay, or overall mortality. However, patients with high-protein intake managed to achieve a better handgrip strength at the end of the 1st week of follow-up. In addition, the quadricep muscle thickness significantly improved with high-protein intake. For future research, we recommend studies with a larger sample size for longer duration of follow-up.

Author contribution

All authors had

1. substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work,

2. drafting the work or revising it critically for important intellectual content,

3. final approval of the version to be published, and

4. agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Financial support and sponsorship


Conflicts of interests

There are no conflicts of interest

  References Top

McClave SA, Taylor BE, Martindale RG, Warren MM, Johnson DR, Braunschweig C, et al; Society of Critical Care Medicine; American Society for Parenteral and Enteral Nutrition. 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. 1
Mehta NM, Skillman HE, Irving SY, Coss-Bu JA, Vermilyea S, Farrington EA, et al. Guidelines for the provision and assessment of nutrition support therapy in the pediatric critically ill patient: Society of Critical Care Medicine and American Society for Parenteral and Enteral Nutrition. Pediatr Crit Care Med 2017;18:675-715.  Back to cited text no. 2
Rennie MJ. Anabolic resistance in critically ill patients. Crit Care Med 2009;37:S398-9.  Back to cited text no. 3
Elke G, van Zanten AR, Lemieux M, McCall M, Jeejeebhoy KN, Kott M, et al. Enteral versus parenteral nutrition in critically ill patients: An updated systematic review and meta-analysis of randomized controlled trials. Crit Care 2016;20:117.  Back to cited text no. 4
Singer P, Blaser AR, Berger MM, Alhazzani W, Calder PC, Casaer MP, et al. ESPEN guideline on clinical nutrition in the intensive care unit. Clin Nutr 2019;38:48-79.  Back to cited text no. 5
Thibault R, Pichard C. Nutrition and clinical outcome in intensive care patients. Curr Opin Clin Nutr Metab Care 2010;13:177-83.  Back to cited text no. 6
Mohialdeen Gubari MI, Hosseinzadeh-Attar MJ, Hosseini M, Mohialdeen FA, Othman H, Hama-Ghareeb KA, et al. Nutritional status in intensive care unit: A meta-analysis and systematic review. Galen Med J 2020;9:e1678.  Back to cited text no. 7
Lew CCH, Wong GJY, Cheung KP, Chua AP, Chong MFF, Miller M. Association between malnutrition and 28-day mortality and intensive care length-of-stay in the critically ill: A prospective cohort study. Nutrients 2017;10:10.  Back to cited text no. 8
Jeejeebhoy KN. Parenteral nutrition in the intensive care unit. Nutr Rev 2012;70:623-30.  Back to cited text no. 9
Iapichino G, Radrizzani D, Solca M, Pesenti A, Gattinoni L, Ferro A, et al. The main determinants of nitrogen balance during total parenteral nutrition in critically ill injured patients. Intensive Care Med 1984;10:251-4.  Back to cited text no. 10
Kim TJ, Park SH, Jeong HB, Ha EJ, Cho WS, Kang HS, et al. Optimizing nitrogen balance is associated with better outcomes in neurocritically ill patients. Nutrients 2020;12:3137.  Back to cited text no. 11
Mendes NP, Barros TA, Faria BS, Aguiar ES, de Oliveira CA, Souza ECG, et al. Hand grip strength as predictor of undernutrition in hospitalized patients with cancer and a proposal of cut-off. Clin Nutr ESPEN 2020;39:210-4.  Back to cited text no. 12
Flood A, Chung A, Parker H, Kearns V, O’Sullivan TA. The use of hand grip strength as a predictor of nutrition status in hospital patients. Clin Nutr 2014;33:106-14.  Back to cited text no. 13
Ali NA, O’Brien JM Jr, Hoffmann SP, Phillips G, Garland A, Finley JC, et al; Midwest Critical Care Consortium. Acquired weakness, handgrip strength, and mortality in critically ill patients. Am J Respir Crit Care Med 2008;178:261-8.  Back to cited text no. 14
Ferrie S, Tsang E. Monitoring nutrition in critical illness: What can we use? Nutr Clin Pract 2018;33:133-46.  Back to cited text no. 15
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
Dresen E, Weißbrich C, Fimmers R, Putensen C, Stehle P. Medical high-protein nutrition therapy and loss of muscle mass in adult ICU patients: A randomized controlled trial. Clin Nutr 2021;40:1562-70.  Back to cited text no. 17
Hunter A, Johnson L, Coustasse A. Reduction of intensive care unit length of stay: The case of early mobilization. Health Care Manag (Frederick) 2014;33:128-35.  Back to cited text no. 18
Arabi YM, Al-Dorzi HM, Mehta S, Tamim HM, Haddad SH, Jones G, et al; PermiT Trial Group. 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. 19
Looijaard WGPM, Dekker IM, Beishuizen A, Girbes ARJ, Oudemans-van Straaten HM, Weijs PJM. Early high protein intake and mortality in critically ill ICU patients with low skeletal muscle area and density. Clin Nutr 2020;39: 2192-201.  Back to cited text no. 20


  [Figure 1], [Figure 2], [Figure 3]

  [Table 1], [Table 2], [Table 3]


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