Early high protein intake is associated with low mortality and energy overfeeding with high mortality in non-septic mechanically ventilated critically ill patients
Open accessAbstract
Introduction: Early protein and energy feeding in critically ill patients is heavily debated and early protein feeding hardly studied. Methods: A prospective database with mixed medical-surgical critically ill patients with prolonged mechanical ventilation (>72 hours) and measured energy expenditure was used in this study. Logistic regression analysis was used to analyse the relation between admission day-4 protein intake group (with cutoffs 0.8, 1.0, and 1.2 g/kg), energy overfeeding (ratio energy intake/measured energy expenditure > 1.1), and admission diagnosis of sepsis with hospital mortality after adjustment for APACHE II (Acute Physiology and Chronic Health Evaluation II) score. Results: A total of 843 patients were included. Of these, 117 had sepsis. Of the 736 non-septic patients 307 were overfed. Mean day-4 protein intake was 1.0 g/kg pre-admission weight per day and hospital mortality was 36%. In the total cohort, day-4 protein intake group (odds ratio (OR) 0.85; 95% confidence interval (CI) 0.73 to 0.99; P = 0.047), energy overfeeding (OR 1.62; 95%CI 1.07 to 2.44; P = 0.022), and sepsis (OR 1.77; 95%CI 1.18 to 2.65; P = 0.005) were independent risk factors for mortality besides APACHE II score. In patients with sepsis or energy overfeeding, day-4 protein intake was not associated with mortality. For non-septic, non-overfed patients (n = 419), mortality decreased with higher protein intake group: 37% for <0.8 g/kg, 35% for 0.8 to 1.0 g/kg, 27% for 1.0 to 1.2 g/kg, and 19% for ≥1.2 g/kg ( P = 0.033). For these, a protein intake level of ≥1.2 g/kg was significantly associated with lower mortality (OR 0.42, 95%CI 0.21 to 0.83, P = 0.013). Conclusions: In non-septic critically ill patients, early high protein intake was associated with lower mortality and early energy overfeeding with higher mortality. In septic patients early high protein intake had no beneficial effect on mortality.
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Weijs et al. found an overall mortality benefit of early high protein intake in non-septic subjects only.
“Weijs et al. [24] prospectively studied 843 critically ill patients and found an overall mortality benefit of early high protein intake in non-septic subjects only.”
From Nutrition in Sepsis: A Bench-to-Bedside Review. (2020) · cites this paper as [24]
The Abstract Results report 843 patients and an association between higher early protein intake and lower hospital mortality in non-septic, non-overfed patients, but not in patients with sepsis or energy overfeeding. The Discussion describes this as a post-hoc observational finding, so “mortality benefit” overstates a causal effect and omits the non-overfed restriction. (LLM, conf=0.87)
Experimental — accuracy not yet measuredHeiddeger et al. (128) measured EE at day 3 and adapted calorie intake, comparing supplemental PN from day four to an EN-only group; the intervention group had a lower late nosocomial infection rate after day 9.
“Heiddeger et al. ( 128) measured EE at day 3 and adapted the calorie intake accordingly, comparing supplemental PN from day four to an EN only group.The intervention group had a lower late nosocomial infection rate after day 9.”
From ESPEN guideline on clinical nutrition in the intensive care unit. (2019) · cites this paper as [128]
The Discussion > Overfeeding (page unavailable) reports that the Swiss trial used calorimetry-tailored energy intake and found fewer infections with supplemental PN from day 4; References identifies that trial as Heidegger et al. Our copy does not specify EE measurement on day 3, an EN-only comparator, or that the reduction concerned late nosocomial infections after day 9. (LLM, conf=0.87)
Experimental — accuracy not yet measuredUndernutrition or over-nutrition is deleterious to outcome according to large observational studies.
“Undernutrition or over-nutrition is deleterious to outcome according to these large observational studies.”
From ESPEN practical and partially revised guideline: Clinical nutrition in the intensive care unit (2023) · cites this paper as [55]
The Results (Non-septic overfed and non-overfed patients; page unavailable) associate early energy overfeeding with higher mortality and higher protein intake with lower mortality in non-septic patients. But the Results (Possible underfeeding effect; page unavailable) do not establish that energy underfeeding worsened mortality: excluding seriously energy-underfed patients strengthened the low-protein mortality contrast. The claim also states these observational associations as though they establish harm. (LLM, conf=0.85)
Experimental — accuracy not yet measuredA larger database analysis suggested that energy intake is associated with significantly improved survival when it is close to measured EE or between 70 and 100% of the repeatedly measured resting EE.
“A larger database analysis suggested that energy intake is associated with significantly improved survival when it is close to measured EE [55] or between 70 and 100% of the repeatedly measured resting EE [56].”
From ESPEN practical and partially revised guideline: Clinical nutrition in the intensive care unit (2023) · cites this paper as [55]
The Results (Possible underfeeding effect; page unavailable) report lower mortality odds at 90–100% of measured EE, but that comparison is between protein-intake groups, not a finding that energy intake near EE independently improves survival. The Discussion (Overfeeding; page unavailable) explicitly says improved energy intake with insufficient protein was not associated with lower mortality. The separate 70–100% claim is attached to citation [56], not this source. (LLM, conf=0.84)
Experimental — accuracy not yet measuredSome other studies addressing supplemental PN did not show similar findings to the EPaNIC study.
“Some of the other studies addressing supplemental PN (128, 154, 155) did not show similar findings to the EPaNIC study.”
From ESPEN guideline on clinical nutrition in the intensive care unit. (2019) · cites this paper as [128]
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- Authors
- Weijs, P. J., Looijaard, W. G., Beishuizen, A., Girbes, A. R., & Oudemans-van Straaten, H. M.
- Affiliations
- Amsterdam University of Applied Sciences (NL)
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- Medisch Spectrum Twente (NL)
- Amsterdam Cardiovascular Sciences (NL)
- Corresponding author
- Weijs, Peter JM
- Venue
- Critical Care
- Published
- 2014-12-14
- Volume
- 18
- Issue
- 6
- Pages
- 701-701
- ISSN
- 1364-8535 (ISSN-L)
- PMC
- PMC4279460
- OpenAlex
- W1981313739
- Cited by
- 358
- References
- 40
- Citations by year
- 2026: 18 · 2025: 17 · 2024: 48 · 2023: 30 · 2022: 35 · 2021: 30 · 2020: 38 · 2019: 43 · 2018: 43 · 2017: 24 · 2016: 26 · 2015: 6
- FWCI
- 17.38
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Critical Care (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, cc-by)
- Pure Amsterdam UMC (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Clinical Nutrition and Gastroenterology
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Keywords
- mechanical ventilation, critically ill patients, sepsis, in-hospital mortality, energy expenditure, protein intake, nutritional support, mortality risk factors, APACHE II score, prolonged mechanical ventilation, intensive care unit patients, mortality prediction model, prognostic factors, prognostic score, prognostic score validation, prognostic score comparison
- MeSH terms
- Adult, Aged, Aged, 80 and over, Energy Intake, Dietary Proteins, Female, Humans, Male, Middle Aged, Prospective Studies, Respiration, Artificial, Cohort Studies, Critical Illness, Hospital Mortality, Overnutrition
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