Optimal delivery of enteral protein in the critically ill: A protocol for a systematic review and meta-analysis of randomised controlled trials

Background: The optimal dose of enteral protein to deliver during critical illness remains uncertain. International clinical practice guidelines recommend protein targets ranging from 1.2 to 2.0 g/kg body weight/day, which is greater than the amount recommended in health. This protocol details the conduct of a systematic review and meta-analysis to evaluate the effect of enteral protein delivered within the international recommended guidelines (1.2–2.0 g/kg/day) compared to less than international recommended guidelines (<1.2 g/kg/day) on mortality and morbidity outcomes. Methods: A systematic review and meta-analysis will be undertaken in accordance with the Cochrane Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 statement. A comprehensive literature search of studies indexed in MEDLINE, EMBASE, CINAHL and Cochrane Central Register of Controlled Trials will be conducted. Studies will be included if they are randomised controlled trials (RCTs) enrolling adult critically ill patients comparing predominately enteral protein delivery with one arm receiving 1.2–2.0 g/kg/day protein/kg/day (‘greater protein’) and another arm receiving <1.2 g protein/kg/day (‘lesser protein’). Two independent reviewers will perform title and full text screening for study inclusion, extract data from included studies, and assess study quality using the Cochrane Risk of Bias 2 tool. The primary outcome will be mortality at 90 days. Secondary outcomes will be clinical (infectious complications, and durations of ICU and hospital stays and mechanical ventilation), patient-centred (discharge destination, physical function and quality of life) and muscle (muscle mass, strength) outcomes. Results: Random-effects meta-analysis will be fitted for all outcomes, and, for the primary outcome, risk ratios will be pooled using a random-effects meta-analysis model and pooled treatment effect presented as risk ratio (95% Confidence Interval). Conclusions: This systematic review and meta-analysis will compile data to determine whether outcomes are optimised with greater or lesser amounts of enteral protein delivered during critical illness. Systematic review registration: CRD42025547923.