# Optimal timing of enteral nutrition initiation in critically ill patients: a network meta-analysis

**Authors:** Ming Dai, Hong-Wei Yang, You Zhou, Qian Guo, Yuan Meng, Yun Lei Sun, Pei-Ya Hu

PMC · DOI: 10.3389/fnut.2026.1722626 · Frontiers in Nutrition · 2026-02-06

## TL;DR

This study compares the best time to start feeding critically ill patients through the gut to improve outcomes like survival and ICU stay.

## Contribution

A network meta-analysis comparing five enteral nutrition initiation timings to identify the most effective window for clinical outcomes in critically ill patients.

## Key findings

- Initiating enteral nutrition within 24–48 hours may be associated with lower mortality.
- Initiating enteral nutrition beyond 96 hours is most likely to shorten ICU length of stay.
- No significant differences in mortality or ICU length of stay were observed between other initiation timings.

## Abstract

Nutritional support is pivotal in managing critically ill patients. Enteral nutrition, which preserves intestinal mucosal barrier function and modulates immune-metabolic homeostasis, is the preferred nutritional support strategy. However, the optimal timing for initiating EN remains controversial: some studies advocate early initiation (within 24–48 h), while others suggest delayed initiation (beyond 48 h), resulting in inconsistent clinical practices and conflicting guideline recommendations. This highlights the need for high-quality evidence to clarify the optimal EN initiation window.

This network meta-analysis aims to systematically compare the effects of five EN initiation timings on key clinical outcomes in critically ill patients, rank their efficacy, and identify the optimal initiation window, thereby providing evidence-based guidance for clinical practice.

We conducted a network meta-analysis following the PRISMA-NMA statement, including randomized controlled trials (RCTs) comparing the five EN initiation timings in critically ill adults. Databases (PubMed, Embase, Web of Science, Cochrane Library) were searched from inception to September 2024. Data analysis was performed using Stata 16.0 and RevMan 5.4, with efficacy ranked via the surface under the cumulative ranking curve (SUCRA).

Fifteen RCTs were included, involving five EN initiation timings: <24 h, 24–48 h, 48–72 h, 72–96 h, and >96 h. No statistically significant differences in mortality or ICU length of stay were observed between any two timings. However, SUCRA ranking showed that 24–48 h initiation had the highest probability of reducing mortality (SUCRA = 67.0), while >96 h initiation was most likely to shorten ICU length of stay (SUCRA = 75.2).

Initiating EN beyond 96 h was associated with the shortest ICU stay, while initiating it within 24–48 h may be associated with lower mortality. Based on the current limited evidence, the 24–48 h window may be relatively optimal for improving clinical outcomes in critically ill patients. However, given the small number of included studies and low to moderate evidence quality, this conclusion requires validation in large, high-quality RCTs.

https://www.crd.york.ac.uk/PROSPERO/view/CRD42024581390. identifier PROSPERO (CRD42024581390).

## Full-text entities

- **Genes:** CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, MADCAM1 (mucosal vascular addressin cell adhesion molecule 1) [NCBI Gene 8174] {aka MACAM1}
- **Diseases:** mortality (MESH:D003643), malnutrition (MESH:D044342), neurological injuries (MESH:D020196), metabolic disturbances (MESH:D024821), Critically ill (MESH:D016638), hepatic dysfunction (MESH:D008107), injury (MESH:D014947), shock (MESH:D012769), acute pancreatitis (MESH:D010195), cerebral malaria (MESH:D016779), traumatic brain injury (MESH:D000070642), gastrointestinal dysfunction (MESH:D005767), ischemic injury (MESH:D017202), enterogenic infections (MESH:D007239), diarrhea (MESH:D003967), aspiration pneumonia (MESH:D011015), gastric retention (MESH:C565114), MODS (MESH:D009102), EN (MESH:D004751), vomiting (MESH:D014839), SAP (MESH:D045169), burns (MESH:D002056), coma (MESH:D003128), intestinal (MESH:D007410), blunt trauma (MESH:D014949), septic shock (MESH:D012772), ischemia (MESH:D007511), immune dysregulation (OMIM:614878)
- **Chemicals:** oxygen (MESH:D010100), vanillylmandelic acid (MESH:D014642), catecholamine (MESH:D002395)
- **Species:** Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116], Cavia porcellus (domestic guinea pig, species) [taxon 10141]

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12920217/full.md

## References

48 references — full list in the complete paper: https://tomesphere.com/paper/PMC12920217/full.md

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Source: https://tomesphere.com/paper/PMC12920217