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.