Impact of protein intervention timings on critically ill patients: A systematic review and meta- analysis.

2025-10-01
Journal of critical care medicine (Universitatea de Medicina si Farmacie din Targu-Mures) 11(4)
- Pranav Kumar Sharma
- Sanjiya Arora
- Tirth Bhavsar
- Mamta Kamboj
- Rahul Kamboj
- Varnika Gupta
- Anitha Sigamani Ramamurthi
- Kumari Uthayakumar
- Ajay Singh
- Sachin Mahendrakumar Chaudhary
- Arghadip Das
- Arianisa Bajrami
- Sumesh Singh
- Devendra Tripathi

PubMed: 41208925
DOI: 10.2478/jccm-2025-0047

Study Design

Type: Review
Sample size: n = 672
Population: adult ICU patients
Methods: Systematic review and meta-analysis of studies comparing early vs late protein administration in adult ICU patients

Background

Critically ill patients experience metabolic alterations that promote muscle atrophy and protein catabolism, increasing morbidity and mortality. While adequate protein provision is essential, the optimal timing remains controversial. Guidelines recommend higher protein targets, but evidence from randomized controlled trials is limited and inconsistent.

Aim

To evaluate the effects of early versus late protein supplementation on mortality, complications, and clinical outcomes in critically ill patients.

Methods

A systematic review and meta-analysis were conducted using PubMed, Embase, Cochrane Library, and Google Scholar (January 2010-December 2022). Studies comparing early and late protein administration in adult ICU patients were included. Primary outcomes were mortality, infectious complications, overall complications, pneumonia, ICU/hospital length of stay, and mechanical ventilation duration.

Results

Thirteen studies (8 RCTs, 3 retrospective, 2 prospective cohorts) involving 10,672 patients were analyzed. Mortality (RR = 0.87, 95% CI: 0.74-1.04, p = 0.11; I² = 36%), overall complications (RR = 0.87, 95% CI: 0.74-1.02, p = 0.08; I² = 26%), infectious complications (RR = 0.86, 95% CI: 0.58-1.27, p = 0.37; I² = 65%), and pneumonia (RR = 0.78, 95% CI: 0.41-1.48, p = 0.34; I² = 0%) showed no significant differences between early protein (EP) and late protein (LP) groups. EP significantly reduced ICU length of stay (MD = -0.28 days, 95% CI: -0.33 to -0.23, p < 0.00001; I² = 99%) and mechanical ventilation duration (MD = -0.66 days, 95% CI: -0.90 to -0.41, p < 0.00001; I² = 85%), but was associated with a longer hospital stay (MD = 0.47 days, 95% CI: 0.31-0.63, p < 0.00001; I² = 98%).

Conclusion

Early protein supplementation does not significantly affect mortality or major complications but may shorten ICU stay and ventilation duration. High heterogeneity for some outcomes warrants cautious interpretation.

Research Insights

Protein→Reduced Duration of Mechanical Ventilation
mechanical ventilation duration (MD = -0.66 days, 95% CI: -0.90 to -0.41, p < 0.00001; I² = 85%)
Effect
Beneficial
Effect size
Small
Protein→Reduced Infectious Complication
infectious complications (RR = 0.86, 95% CI: 0.58-1.27, p = 0.37; I² = 65%) ... showed no significant differences
Effect
Neutral
Effect size
Small
Protein→Reduced Length of Hospital Stay
was associated with a longer hospital stay (MD = 0.47 days, 95% CI: 0.31-0.63, p < 0.00001; I² = 98%)
Effect
Harmful
Effect size
Small
Protein→Reduced Length of Stay
EP significantly reduced ICU length of stay (MD = -0.28 days, 95% CI: -0.33 to -0.23, p < 0.00001; I² = 99%)
Effect
Beneficial
Effect size
Small
Protein→Reduced Mortality Risk
Mortality (RR = 0.87, 95% CI: 0.74-1.04, p = 0.11; I² = 36%) ... showed no significant differences between early protein (EP) and late protein (LP) groups.
Effect
Neutral
Effect size
Small
Protein→Reduced Overall Complication
overall complications (RR = 0.87, 95% CI: 0.74-1.02, p = 0.08; I² = 26%) ... showed no significant differences
Effect
Neutral
Effect size
Small
Protein→Reduced Pneumonia Rate
pneumonia (RR = 0.78, 95% CI: 0.41-1.48, p = 0.34; I² = 0%) showed no significant differences
Effect
Neutral
Effect size
Small