Effect of early parenteral nutrition versus enteral nutrition alone on all‐cause mortality in critically ill adults: A systematic review and meta‐analysis

Abstract Background For nutritional support in critically ill patients, the early initiation of enteral nutrition (EN) in the presence of gastrointestinal function has been agreed upon by most scholars. However, EN support alone cannot fully meet the needs of the body in some cases, so considering supplemental parenteral nutrition (SPN) become the solution to meet patients’ energy target. However, there is no consensus on whom and when parenteral nutrition should be considered in critically ill patients as a total form of nutrition. So, we aimed to compare and evaluate the effect of early PN on the outcome and their safety in critically ill adults. Methods Randomized controlled trials (RCTs) were retrieved from PubMed, Embase, Cochrane Library, and Web of Science (up to March 2024). Adults with critical illness treated with total parenteral nutrition (TPN) or SPN versus EN alone were enrolled. We screened studies and extracted data independently. The primary outcome was all-cause mortality which was evaluated by pooled risk ratio (RR) with the fixed-effects model. The risk of bias was evaluated using Cochrane risk bias of tool and a meta-analysis was conducted using RevMan 5.4 software. This study was prospectively registered in PROSPERO database (CRD42023462386). Results Twenty RCTs enrolling 11303 patients were eligible. No significant disparities were observed in 30-day all-cause mortality (relative risk [RR] 0.96, 95% confidence interval [CI] 0.90–1.03, P = 0.29), hospital mortality (RR 0.96, 95% CI 0.90–1.02, P = 0.17), or 90-day mortality (RR 0.95, 95% CI 0.86–1.04, P = 0.26) between the PN (TPN or SPN) and enteral nutrition (EN) alone groups. However, the use of PN in conjunction with EN was associated with a reduced ICU mortality rate compared to EN alone (RR 0.92, 95% CI 0.86–0.99, P = 0.03). PN therapy was linked to a modest elevation in the risk of infection (RR 1.12, 95% CI 1.05–1.21, P = 0.002), predominantly due to bloodstream infections (RR 1.24, 95% CI 1.08–1.51, P = 0.005). Additionally, PN was associated with a significant reduction in the duration of mechanical ventilation (standardized mean difference [SMD] = -1.47, 95% CI -2.72 to -0.23, P = 0.02) and a decreased incidence of gastrointestinal intolerance events (RR 0.85, 95% CI 0.77–0.94, P = 0.002). Conclusion Administration of PN can reduce ICU mortality, duration of mechanical ventilation and gastrointestinal intolerance events, although it increases total infection especially bloodstream infection rate among critically ill patients. More studies are warranted to confirm these findings.