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

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.

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

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.

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%).

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.