Higher Versus Lower Protein Delivery in Critically Ill Patients: A Systematic Review and Bayesian Meta-Analysis.

OBJECTIVES

Recent multicenter trials suggest that higher protein delivery may result in worse outcomes in critically ill patients, but uncertainty remains. An updated Bayesian meta-analysis of recent evidence was conducted to estimate the probabilities of beneficial and harmful treatment effects.

DATA SOURCES

An updated systematic search was performed in three databases until September 4, 2024. The study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines and the protocol was preregistered in PROSPERO (CRD42024546387).

STUDY SELECTION

Randomized controlled trials that studied adult critically ill patients comparing protein doses delivered enterally and/or parenterally with similar energy delivery between groups were included.

DATA EXTRACTION

Data extraction was performed by two authors independently, using a predefined worksheet. The primary outcome was mortality. Posterior probabilities of any benefit (relative risk [RR] < 1.00) or harm (RR > 1.00) and other important beneficial and harmful effect size thresholds were estimated. Risk of bias assessment was performed using the risk of bias 2.0 tool. All analyses were performed using a Bayesian hierarchical random-effects models, under vague priors.

DATA SYNTHESIS

Twenty-two randomized trials ( n = 4164 patients) were included. The mean protein delivery in the higher and lower protein groups was 1.5 ± 0.6 vs. 0.9 ± 0.4 g/kg/d. The median RR for mortality was 1.01 (95% credible interval, 0.84-1.16). The posterior probability of any mortality benefit from higher protein delivery was 43.6%, while the probability of any harm was 56.4%. The probabilities of a 1% (RR < 0.99) and 5% (RR < 0.95) mortality reduction by higher protein delivery were 38.7% and 22.9%, respectively. Conversely, the probabilities of a 1% (RR > 1.01) and 5% (RR > 1.05) mortality increase were 51.5% and 32.4%, respectively.

CONCLUSIONS

There is a considerable probability of an increased mortality risk with higher protein delivery in critically ill patients, although a clinically beneficial effect cannot be completely eliminated based on the current data.