Protein Requirements in the Critically Ill: A Randomized
Controlled Trial Using Parenteral Nutrition

Ferrie. Journal Parenter Enteral Nutr 2016;40:795-805. doi: 10.1177/0148607115618449

Clinical Question

  •  In critically ill adult patients receiving parenteral nutrition, does high amino acid intake compared with standard level amino acid intake, result in greater hand grip strength at ICU discharge?


  • Randomised controlled trial
  • Consecutively numbered sealed opaque envelopes with weekly auditing to ensure allocation concealment maintained
  • Varying block size
  • Double blind
  • Power calculation
    • 96 participants were required at a power of 80% and an alpha of 0.05 to detect a 6kg difference in hand grip strength between the two groups, from a baseline grip strength of 14.68kg
    • Recruitment goal increased to 120 patients prior to study commencement to allow for dropouts
  • Primary outcome changed prior to study commencement from nitrogen balance to handgrip strength due to the concern with missing data if nitrogen balance was used


  • Single centre tertiary mixed medical/surgical ICU, Australia
  • Data collected over 12 months from 2013-2014


  • Inclusion criteria: All patients admitted to the ICU who required parental nutrition (PN)
  • Exclusion criteria: Younger than 16 years old; were not expected to require intervention for at least 3 days; had recently received significant nutrition in past 3 days via enteral nutrition (EN) or PN
  • 217 patients were screened, 137 were approached for inclusion, 120 were randomised
  • Comparing baseline characteristics of high protein vs. standard protein groups – no significant differences
    • Median age: 67.0 vs. 64.5
    • APACHE II score: 25.5 vs. 23.7
    • SOFA score: 9.4 vs. 9.2
    • Nutritional risk screening 2002 score : 4.3 vs. 3.9


  • High protein parenteral nutrition – daily amino acid target of 1.2g/kg
    • Baxter Olimel N9
      • 1070 calories/litre
      • 9g protein/litre
      • 57g amino acids/litre


  • Standard protein parenteral nutrition – daily amino acid target of 0.8g/kg
    • Oli-Clinomel N7
      • 1200 calories/litre
      • 40g protein/litre
      • 7 grams amino acids/litre

Common management

  • PN solution delivered for 10 days or until ICU discharge
  • PN delivered via central line
  • Vitamins and trace elements provided to meet Australian recommendations
  • Nutrition assessment conducted by the dietitian, with an energy aim of 26 kcal/kg in the lower protein group and 24 kcal/kg in the higher protein group.
  • Current body weight was used for patients with a BMI between 20-30 kg/m2, and adjusted to 20 kg/m2 for underweight and 27.5 kg/m2 for overweight patients
  • Anthropometric measurements were standardised and completed by the same researcher for internal validity.

Comparing nutrition achieved during study period between high protein and standard protein groups:

  • Days on parental nutrition (median): 9.5 vs. 10
  • Calories – significantly less in high protein group
    • Per day in 1st 3 days: 23.5 vs. 26.0, p=0.002
    • Per day in 1st 7 days: 23.1 vs. 24.9, p=0.001
  • Amino acids – significantly more in high protein group
    • Per day in 1st 3 days: 1.17g/kg vs. 0.87g/kg, p<0.001
    • Per day in 1st 7 days: 1.09g/kg vs. 0.90g/kg, p<0.001


  • Primary outcome: Hand grip strength at ICU discharge – no significant difference
    • Comparing high protein vs. standard protein group
      • 18.5kg (10.4 Standard deviation) vs. 15.8 (10.3SD) kg, p=0.054
      • 10% of patients lost to follow-up
  • Secondary outcomes:
    • Comparing high protein vs. standard protein groups
      • Hand grip strength at day 7 – significantly improved in high protein group
        • 22.1kg (10.1 SD) vs. 18.5kg (11.8 SD), 0=0.025
      • Nitrogen balance
        • At day 3 – significantly less in standard protein group
          • -0.5g/d vs. -5.6g/d, p<0.0001
        • At day 7 – no significant difference
          •  -4.9g/d vs. -4.7g/d, p=0.92
      • Fatigue score at day 7 (Chalder scale) – significantly reduced  in high protein group
        • 5.4 vs. 6.2, p=0.045
      • Sum of 3 muscle sites on ultrasound on day 7 – significantly higher in high protein group
        • 8.4cm vs. 7.9cm, p=0.02
      • Ventilator days – no significant difference
        • 2 vs. 2
      • ICU mortality – no significant difference
        • 8% vs. 6%, p=0.55

Authors’ Conclusions

  • The delivery of higher amino acids to critically ill patients demonstrated small differences in various measures that may be clinically meaningful


  • This is the first RCT on this topic
  • Appropriate randomisation method and concealment of allocation has minimised selection bias
  • It has include a suite of functional and nutrition status outcome measures which may be important for future nutrition trials
  • Double blinded
  • Recorded energy/protein from other sources e.g. enteral nutrition, propofol


  • The trial did not achieve the target amino acid delivery difference between the two groups, thus, the actual difference in amino acid delivery was small.
  • There was an energy delivery difference between the 2 groups, particularly in the first 3 days. As energy and protein are likely to have a synergistic effect, this is difficult to interpret how this might affect the results.
  • There was a significant loss of data at discharge for primary and secondary outcome variables. This highlights the difficulty in getting such measures in ICU nutrition or function trials.
  • Single centre
  • Change in primary outcome

The Bottom Line

  • In critically ill adults patients receiving parenteral nutrition, this trial did not show any difference in hand grip strength at ICU discharge, with amino acid delivery of 1.1g/kg vs 0.9g/kg.  Changes in other outcomes were minor, with differences disappearing later in ICU admission or failing to reach statistical significance. This is a small study and practice changes can not be recommended. It will be interesting to explore in larger trials if any of these changes in functional or muscle outcomes reach clinical or statistical significance. A very hot topic for the future.

External Links


Summary author: Emma Ridley
Summary date: 17th April 2017
Peer-review editor: @davidslessor

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