The effects of higher or lower protein delivery on outcomes for mechanically ventilated critically ill patients:a systematic review and meta-analysis of randomized controlled trials

Abstract Background Pronounced variations in protein dosing recommendations are evident across sets of international guidelines for critically ill patients. To survey extant randomized controlled trial (RCT) data, the present article was formulated as a systematic review and meta-analysis aimed at comparing the effects of lower and higher levels of protein delivery on outcomes for mechanically ventilated critically ill patients. Methods The PubMed, Embase, Web of SCI, and Cochrane Library databases were searched for all relevant RCTs published as of May 16, 2023. Eligible RCTs were those that (1) enrolled critically ill individuals ≥ 18 years of age that were mechanically ventilated; (2) enrolled patients with an intensive care unit (ICU) length of stay ≥ 3 days; (3) included comparisons of protein doses; (4) reported similar energy intake levels among groups; and (5) included a discussion of clinical and/or patient-centered outcomes. Screening and quality analyses were independently performed by two investigators. Pooled risk ratios and mean difference values were then estimated for categorical and continuous variables random-effects meta-analyses. Results In total, 12 RCTs enrolled 2286 patients were included in these analyses. All 12 studies reported on mechanical ventilation duration and mortality. Overall mortality (RR 0.90, 95% CI 0.72–1.12, P = 0.33; I 2 = 26%), the duration of mechanical ventilation (MD 0, 95%CI -0.58-0.58, P = 0.99; I 2 = 0%), and other patient-centered outcomes were unaffected by the level of protein delivery. Subgroup analyses, however, suggested that higher levels of protein delivery with early exercise were associated with a reduced risk of in-ICU mortality (RR 0.63, 95% CI 0.42–0.94, P = 0.02; I 2 = 0%). Conclusion These results suggest that higher levels of protein delivery have no significant impact on the clinical or patient-centered outcomes for mechanically ventilated critically ill patients. However, combining higher levels of protein delivery and early exercise may contribute to better patient outcomes, although additional RCTs will be necessary to confirm this possibility. PROSPERO registration: CRD42023423246(16/05/2023)