TL;DR: 🟡 Positive, but outlier — this smaller single-center trial found early high protein reduced mortality, directly contradicting the much larger PRECISe trial (this handbook) — weigh PRECISe more heavily.
1. Publication
- Title: Impact of early high protein intake in critically ill patients: a randomized controlled trial
- Acronym: None assigned
- Year & Journal: Nutrition & Metabolism (London), published June 28, 2024 (21:39)
- Citation: Wang Y, Ye Y, Xuan L, et al. Nutr Metab (Lond). 2024;21:39. doi:10.1186/s12986-024-00818-8
2. Context & Rationale
Background: Prior evidence on early high protein intake in critical illness is conflicting — notably contrasting with the much larger PRECISe trial (this handbook), which found harm from high protein. ASPEN and ESPEN guidelines recommend more protein than healthy individuals need, but the optimal early-phase dose remains actively debated.
Research Question/Hypothesis: In critically ill patients with high nutritional risk (mNUTRIC>5) and expected ICU stay >7 days, does early high protein intake (1.5 g/kg/day vs 0.8 g/kg/day) improve 28-day mortality and other clinical outcomes?
3. Design & Methods
- Study Type: Single-center (with multi-institutional authorship) randomized controlled trial
- Setting & Centers: China (Zhuji Traditional Chinese Medical Hospital and collaborators)
- Population: 173 critically ill ICU/EICU patients, mNUTRIC>5, expected stay >7 days
- Intervention: High protein — 1.5 g/kg/day within days 1-3 of enteral nutrition (n=86)
- Comparator: Low protein — 0.8 g/kg/day within days 1-3 (n=87); both groups transitioned to 1.5 g/kg/day on day 4
- Statistical Power & Follow-Up: Primary: 28-day mortality. Secondary: MV duration, ICU stay, refeeding syndrome, EN tolerance, prealbumin, rectus femoris muscle thickness.
4. Key Results
173 patients randomized (87 low, 86 high).
Outcome | High Protein (1.5 g/kg/d early) | Low Protein (0.8 g/kg/d early) | Effect Size | 95% CI | p-value | Notes |
28-day mortality (primary) | Lower | Higher | HR 2.462 (Low vs High) | 1.021–5.936 | 0.045 | Significant benefit with early high protein |
MV duration, ICU stay | Shorter | Longer | — | — | Significant | Favored high protein |
Serum prealbumin | Higher | Lower | — | — | — | Favored high protein |
Rectus femoris muscle atrophy | Lower | Higher | — | — | — | Favored high protein |
Refeeding syndrome, EN tolerance | No significant difference | No significant difference | — | — | — | No safety penalty |
Septic patient subgroup (n=34) | Significantly lower mortality | — | — | — | — | Small subgroup, hypothesis-generating |
5. Internal Validity Assessment
Single-center (with broader authorship network), modestly sized (173-patient) RCT. Overall: Moderate — statistically significant primary result, but the modest sample size, single-center design, and striking contrast with the much larger, more rigorous PRECISe trial (this handbook, harm signal from high protein) mean this result should be interpreted cautiously and is unlikely to outweigh PRECISe's larger, better-designed evidence.
6. External Validity Assessment
Single Chinese hospital population, high nutritional-risk ICU/EICU patients — limited generalizability given the single-center design and modest sample size.
7. Strengths & Limitations
Strengths: Addresses a genuinely debated question with objective muscle-mass (rectus femoris) and biochemical (prealbumin) secondary measures alongside clinical outcomes.
Limitations: Single-center, modest sample size (173); starkly contrasts with the much larger, double-blind, multicenter PRECISe trial (this handbook) which found the opposite direction of effect (harm from high protein); this trial's positive mortality signal, while statistically significant, comes from a smaller, potentially less generalizable dataset.
8. Interpretation & Practice Impact
Suggests early high protein intake (1.5 g/kg/day) may be safe and beneficial in this specific, high-nutritional-risk single-center population — but this finding directly contradicts the much larger, more rigorous PRECISe trial, and should be weighed accordingly; the field's overall evidence (PRECISe, EFFORT Protein, TARGET Protein) leans toward no benefit or harm from higher protein dosing.
9. Controversies & Subsequent Evidence
This trial is explicitly cited in a broader narrative review ("Protein nutritional support in critically ill patients," Frontiers 2026) alongside a Bayesian meta-analysis (Heuts et al., Crit Care Med 2024) that collectively frames the field as having "conflicting findings" — this study represents one of the smaller, positive outliers in a literature otherwise dominated by larger neutral-to-harmful trials (PRECISe, EFFORT Protein, TARGET Protein).
10. Summary & Executive Takeaway
Summary: This single-center Chinese RCT randomized 173 high-nutritional-risk critically ill patients to early high (1.5 g/kg/day) or low (0.8 g/kg/day) protein intake during days 1-3 of enteral nutrition. The high-protein group had significantly lower 28-day mortality, shorter MV duration/ICU stay, and better muscle/biochemical markers, with no safety penalty.
Overall Takeaway: This smaller, single-center trial found early high protein intake beneficial — a notable outlier contrasting sharply with the much larger, more rigorous PRECISe trial (this handbook) that found harm from high protein delivery; readers should weigh the totality of evidence (favoring PRECISe's larger, more definitive design) rather than this study in isolation when making practice decisions.
11. Bibliography
- Bels JLM, et al. PRECISe. Lancet. 2024;404(10453):659-669 (this handbook).
- Heuts S, Lee ZY, Lew CCH, et al. Higher versus lower protein delivery in critically ill patients: Bayesian meta-analysis. Crit Care Med. 2024;53:e645-e655.