The effect of higher versus lower protein delivery in critically ill patients: a systematic review and meta-analysis of randomized controlled trials

 

The effect of higher versus lower protein delivery in critically ill patients: a systematic review and meta-analysis of randomized controlled trials

 

by Zheng-Yii Lee, Cindy Sing Ling Yap, M. Shahnaz Hasan, Julia Patrick Engkasan, Mohd Yusof Barakatun-Nisak, Andrew G. Day, Jayshil J. Patel and Daren K. Heyland 

 

Critical Care volume 25, Article number: 260, Published: 23 July 2021

Background

The optimal protein dose in critical illness is unknown. We aim to conduct a systematic review of randomized controlled trials (RCTs) to compare the effect of higher versus lower protein delivery (with similar energy delivery between groups) on clinical and patient-centered outcomes in critically ill patients.

Methods

We searched MEDLINE, EMBASE, CENTRAL and CINAHL from database inception through April 1, 2021.We included RCTs of (1) adult (age ≥ 18) critically ill patients that (2) compared higher vs lower protein with (3) similar energy intake between groups, and (4) reported clinical and/or patient-centered outcomes. We excluded studies on immunonutrition. Two authors screened and conducted quality assessment independently and in duplicate. Random-effect meta-analyses were conducted to estimate the pooled risk ratio (dichotomized outcomes) or mean difference (continuous outcomes).

Results

Nineteen RCTs were included (n = 1731). Sixteen studies used primarily the enteral route to deliver protein. Intervention was started within 72 h of ICU admission in sixteen studies. The intervention lasted between 3 and 28 days. In 11 studies that reported weight-based nutrition delivery, the pooled mean protein and energy received in higher and lower protein groups were 1.31 ± 0.48 vs 0.90 ± 0.30 g/kg and 19.9 ± 6.9 versus 20.1 ± 7.1 kcal/kg, respectively. Higher vs lower protein did not significantly affect overall mortality [risk ratio 0.91, 95% confidence interval (CI) 0.75–1.10, p = 0.34] or other clinical or patient-centered outcomes. In 5 small studies, higher protein significantly attenuated muscle loss (MD −3.44% per week, 95% CI −4.99 to −1.90; p < 0.0001).

Conclusion

In critically ill patients, a higher daily protein delivery was not associated with any improvement in clinical or patient-centered outcomes. Larger, and more definitive RCTs are needed to confirm the effect of muscle loss attenuation associated with higher protein delivery.

PROSPERO registration number: CRD42021237530

The Effect of IV Amino Acid Supplementation on Mortality in ICU Patients May Be Dependent on Kidney Function: Post Hoc Subgroup Analyses of a Multicenter Randomized Trial

The Effect of IV Amino Acid Supplementation on Mortality in ICU Patients May Be Dependent on Kidney Function: Post Hoc Subgroup Analyses of a Multicenter Randomized Trial

by Zhu, Ran; Allingstrup, Matilde J.; Perner, Anders; Doig, Gordon S.; for the Nephro-Protective Trial Investigators Group  

Critical Care Medicine: August 2018 - Volume 46 - Issue 8 - p 1293–1301

Objectives: We investigated whether preexisting kidney function determines if ICU patients may benefit from increased (2.0 g/kg/d) protein intake. Design: Post hoc, hypothesis-generating, subgroup analysis of a multicenter, phase 2, randomized clinical trial. All analyses were conducted by intention to treat and maintained group allocation. Ninety-day mortality was the primary outcome. Setting: ICUs of 16 hospitals throughout Australia and New Zealand. Patients: Adult critically ill patients expected to remain in the study ICU for longer than 2 days. Interventions: Random allocation to receive a daily supplement of up to 100 g of IV amino acids to achieve a total protein intake of 2.0 g/kg/d or standard nutrition care. Measurements and Main Results: A total of 474 patients were randomized: 235 to standard care and 239 to IV amino acid supplementation. There was a statistically significant interaction between baseline kidney function and supplementation with study amino acids (p value for interaction = 0.026). Within the subgroup of patients with normal kidney function at randomization, patients who were allocated to receive the study amino acid supplement were less likely to die before study day 90 (covariate-adjusted risk difference, –7.9%; 95% CI, –15.1 to –0.7; p = 0.034). Furthermore, amino acid supplementation significantly increased estimated glomerular filtration rate in these patients (repeated-measures treatment × time interaction p = 0.009). Within the subgroup of patients with baseline kidney dysfunction and/or risk of progression of acute kidney injury, a significant effect of the study intervention on mortality was not found (covariate-adjusted risk difference, –0.6%; 95% CI, –16.2 to 15.2; p = 0.95). Conclusions: In this post hoc, hypothesis-generating, subgroup analysis, we observed reduced mortality and improved estimated glomerular filtration rate in ICU patients with normal kidney function who were randomly allocated to receive increased protein intake (up to 2.0 g/kg/d). We strongly recommend confirmation of these results in trials with low risk of bias before this treatment is recommended for routine care.

Protein in nutrition support: the newborn hero for the critically ill?

Protein in nutrition support: the newborn hero for the critically ill?  Critical Care 2014, 18: 592

Oshima, T., et al.

http://ccforum.com/content/18/6/592

In their current review, Weijs and colleagues highlight the importance of protein and amino acid provision for improving clinical outcome in critically ill patients. The interdependence between energy and protein is highlighted. They call for urgent research to develop new methods to evaluate protein and amino acid requirements, accurately and conveniently, in order to optimize nutrition support for critically ill patients. Appropriate nutrition delivery for critically ill patients remains a highly debated issue. Energy, a critical factor for life, was until now the superstar of nutrition support. It now faces a rival or, more correctly, a partner in function, namely protein. This is a chance to take a close look at protein, the new hero in the field of critical care nutrition, and the struggles it encounters in becoming the true superstar.