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Early versus Late Parenteral Nutrition in Critically Ill Adults
Open accessAbstract
BACKGROUND: Controversy exists about the timing of the initiation of parenteral nutrition in critically ill adults in whom caloric targets cannot be met by enteral nutrition alone. METHODS: In this randomized, multicenter trial, we compared early initiation of parenteral nutrition (European guidelines) with late initiation (American and Canadian guidelines) in adults in the intensive care unit (ICU) to supplement insufficient enteral nutrition. In 2312 patients, parenteral nutrition was initiated within 48 hours after ICU admission (early-initiation group), whereas in 2328 patients, parenteral nutrition was not initiated before day 8 (late-initiation group). A protocol for the early initiation of enteral nutrition was applied to both groups, and insulin was infused to achieve normoglycemia. RESULTS: Patients in the late-initiation group had a relative increase of 6.3% in the likelihood of being discharged alive earlier from the ICU (hazard ratio, 1.06; 95% confidence interval [CI], 1.00 to 1.13; P=0.04) and from the hospital (hazard ratio, 1.06; 95% CI, 1.00 to 1.13; P=0.04), without evidence of decreased functional status at hospital discharge. Rates of death in the ICU and in the hospital and rates of survival at 90 days were similar in the two groups. Patients in the late-initiation group, as compared with the early-initiation group, had fewer ICU infections (22.8% vs. 26.2%, P=0.008) and a lower incidence of cholestasis (P<0.001). The late-initiation group had a relative reduction of 9.7% in the proportion of patients requiring more than 2 days of mechanical ventilation (P=0.006), a median reduction of 3 days in the duration of renal-replacement therapy (P=0.008), and a mean reduction in health care costs of €1,110 (about $1,600) (P=0.04). CONCLUSIONS: Late initiation of parenteral nutrition was associated with faster recovery and fewer complications, as compared with early initiation. (Funded by the Methusalem program of the Flemish government and others; EPaNIC ClinicalTrials.gov number, NCT00512122.).
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“In this circumstance, it is becoming likely that nutrition support may even delay healing due to potential interference with clearance of damage.150, 151, 152”
From Hypoalbuminemia: Pathogenesis and Clinical Significance (2019) · cites this paper as [150]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Late, as compared with early initiation of PN, was associated with lower mortality, less need for ventilation and renal support, shorter ICU and hospital stay, and fewer infectious complications [36].”
From Nutrition in Sepsis: A Bench-to-Bedside Review. (2020) · cites this paper as [36]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Casaer et al. (16) observed that early (supplemental or exclusive) PN is associated with increased morbidity including prolonged ICU dependency and mechanical ventilation, and increased infection rate and need for renal replacement therapy.”
From ESPEN guideline on clinical nutrition in the intensive care unit. (2019) · cites this paper as [16]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In a sub-group analysis of the EPaNIC study, early and late PN was compared in complicated pulmonary/esophageal and abdomino-pelvic surgery patients.Reduced infection rates in late vs early PN were observed (29.9% vs. 40.2%,p=0.01) with no difference in any mortality outcomes, whereas all these patients received virtually no EN during the seven study days (16).”
From ESPEN guideline on clinical nutrition in the intensive care unit. (2019) · cites this paper as [16]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Casaer et al. [14] observed that early (supplemental or exclusive) PN is associated with increased morbidity including prolonged ICU dependency and mechanical ventilation, and increased infection rate and need for renal replacement therapy.”
From ESPEN practical and partially revised guideline: Clinical nutrition in the intensive care unit (2023) · cites this paper as [14]
Experimental — accuracy not yet measured
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Reduced infection rates in late vs early PN were observed (29.9% vs. 40.2%,p ¼ 0.01) with no difference in any mortality outcomes, whereas all these patients received virtually no EN during the seven study days [14].”
From ESPEN practical and partially revised guideline: Clinical nutrition in the intensive care unit (2023) · cites this paper as [14]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Adding parenteral nutrition to enteral nutrition to increase intakes was associated with longer ICU stays and higher infection rates.13,14”
The cited source says what the claim attributes to it.
In the citing paper
“In the EpaNIC randomised trial of early versus late parenteral nutrition to supplement insufficient enteral intakes, mortality was similar in the two groups, but benefits in the late group included fewer ICU-acquired infections and shorter durations of mechanical ventilation, renal replacement therapy, and ICU stay.13”
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“the toleration of a nutritional deficit during the first week of critical illness resulted in fewer complications and accelerated recovery [91].”
From An update on non-thyroidal illness syndrome (2021) · cites this paper as [91]
The cited source says what the claim attributes to it.
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“In our trial, ICU-acquired infections were less common than in EpaNIC despite greater critical illness severity and higher mortality of patients, perhaps because all infections were adjudicated by an independent committee.”
The cited source says what the claim attributes to it.
In the citing paper
“In previous randomised trials, nutritional interventions affected time to readiness for ICU discharge but not mortality.13,14”
The cited source says what the claim attributes to it.
In the citing paper
“A similar strategy regarding this endpoint has been used previously in studies on nutrition in the ICU.13,14”
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In the citing paper
“However, results of this study revealed the potential harm of nutritional intervention aiming at full, possibly overestimated calorie targets during the acute phase of critical illness.”
From ESPEN guideline on clinical nutrition in the intensive care unit. (2019) · cites this paper as [16]
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In the citing paper
“This was also the conclusions of the EPaniC study including more than 1000 septic patients (16).”
From ESPEN guideline on clinical nutrition in the intensive care unit. (2019) · cites this paper as [16]
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“Additionally, one study showed possible benefit of a further delay of PN if EN is not possible/tolerated in non-malnourished ICU patients (16).”
From ESPEN guideline on clinical nutrition in the intensive care unit. (2019) · cites this paper as [16]
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“Additionally, one study showed possible benefit of a further delay of PN if EN is not possible/ tolerated [14].”
From ESPEN practical and partially revised guideline: Clinical nutrition in the intensive care unit (2023) · cites this paper as [14]
The cited source says what the claim attributes to it.
In the citing paper
“However, results of this study revealed the potential harm of nutritional intervention aiming at full, possibly overestimated calorie targets during the acute phase of critical illness.”
From ESPEN practical and partially revised guideline: Clinical nutrition in the intensive care unit (2023) · cites this paper as [14]
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The role of body image changes in neurorehabilitation outcomes: a preliminary study
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“between body representation and nutrition in ABI patients has not been analysed sufficiently (Casaer et al., 2011; Heidegger et al., 2013), we believe that this could be a Table 2.”
BackgroundNutrition delivery after emergency laparotomy in surgical ward: a retrospective cohort study
Nurkkala, J., Lahtinen, S., Ylimartimo, A. T., Kaakinen, T. I., Vakkala, M. A., Koskela, M., & Liisanantti, J. H. (2021) · European Journal of Trauma and Emergency Surgery · doi:10.1007/s00068-021-01659-3 · Cited by 8
“A reason for this might be that nutritional support is more common in the ICU setting than in surgical ward since the majority of ICU patient’s nutrition is commenced by nutritional support [17].”
BackgroundWebbe, J., Battersby, C., Longford, N. T., Ougham, K., Uthaya, S. N., Modi, N., & Gale, C. (2022) · BMJ Paediatrics Open · doi:10.1136/bmjpo-2022-001543 · Cited by 8
The Metabolomics of Critical Illness
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Ernährungspraxis auf Intensivstationen: nutritionDay 2007–2021
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“The EPaNIC trial showed that early 68 parenteral nutrition, as low as 20% of daily calorie needs during the first 24 hrs, was associated with in-69 creased organ dysfunction and increased length of stay in the intensive care unit in critically ill patients 70 (Casaer et al. 2011).”
MethodAre prospective cohort studies an appropriate tool to answer clinical nutrition questions?
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Provision of Nutrients to the Acutely Ill. Introducing the “Baby Stomach” Concept
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The Japanese Clinical Practice Guideline for acute kidney injury 2016
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“However, whether this relationship is causal or merely reflective of more severe insulin resistance in sicker patients remains debated, since randomized controlled trials (RCTs) have yielded at first sight contradictory results [5–12].”
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Drug shortages as an impetus to improve parenteral nutrition practices
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Do we need an assessment of the nutrition risk in the critically ill patient?
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Glycemic Control and Nutrition
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“Immunonutrition” Has Failed to Improve Peritonitis-Induced Septic Shock in Rodents
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Nutritional Status, Assessment, Requirements and Adequacy of Traumatic Brain Injury Patients
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Dyck, L. V., Derese, I., Perre, S. V., Wouters, P. J., Casaer, M. P., Hermans, G., den Berghe, G. V., & Vanhorebeek, I. (2019) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2019-00842 · Cited by 8
Self-citationEarly versus late parenteral nutrition for critically ill term and late preterm infants
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Cost-effectiveness of nutrition therapy
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Nutrition for Critically Ill Patients
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Oral nitrate preparations: an update.
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Blood glucose control in the ICU: how tight?
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“Recently, two large multicenter RCTs have shown that this feeding strategy, which iatrogenically increases the risk of hyperglycemia, is harmful (18,19).”
BackgroundSupplemental parenteral nutrition in critically ill patients
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C-reactive protein in immunometabolism: spared from ‘paying the piper’
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Why Critically Ill Patients Are Protein Deprived
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Nutritional Support in Critically Ill Trauma Patients
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The kidney: the critical organ system for guiding nutrition therapy in the ICU-patient?
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“This was seen in several investigations and also found in the much-cited EPaNIC study from 2011, which compared PN started early versus later [35].”
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“The primary outcome, 90-day all-cause mortality, was analyzed with Kaplan–Meier survival curves stratified by transition status at predefined landmark days ([3, 5, 7], and [10]), with differences assessed by the log-rank test.”
InfluentialFloh, A. A., McCrindle, B. W., Manlhiot, C., Nakada, M., Rotta, G. L., Arsdell, G. V., & Schwartz, S. M. (2019) · Journal of Parenteral and Enteral Nutrition · doi:10.1002/jpen.1529 · Cited by 7
Metadata
- Authors
- Casaer, M. P., Mesotten, D., Hermans, G., Wouters, P. J., Schetz, M., Meyfroidt, G., Van Cromphaut, S., Ingels, C., Meersseman, P., Muller, J., Vlasselaers, D., Debaveye, Y., Desmet, L., Dubois, J., Van Assche, A., Vanderheyden, S., Wilmer, A., & Van den Berghe, G.
- Affiliations
- KU Leuven (BE)
- Jessa Hospital (BE)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2011-08-11
- Volume
- 365
- Issue
- 6
- Pages
- 506-517
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2162310928
- Semantic Scholar
- 43f68b96b74375a705c7271a7c056f6279b2a02c
- Cited by
- 1,696
- References
- 63
- Citations by year
- 2026: 85 · 2025: 102 · 2024: 99 · 2023: 77 · 2022: 82 · 2021: 111 · 2020: 119 · 2019: 107 · 2018: 101 · 2017: 123 · 2016: 115 · 2015: 154 · 2014: 162 · 2013: 135 · 2012: 93
- FWCI
- 122.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Lirias (submittedVersion)
- Funders
- Fonds Wetenschappelijk Onderzoek
- Vlaamse regering
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Clinical Nutrition and Gastroenterology
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Health Sciences › Medicine › Surgery › Enhanced Recovery After Surgery
- Keywords
- parenteral nutrition, timing of parenteral nutrition initiation, critically ill adults, intensive care unit, enteral nutrition, insulin infusion, normoglycemia, intensive care unit discharge, hospital discharge, cholestasis, mechanical ventilation duration, renal replacement therapy, health care costs, functional status
- MeSH terms
- Adult, Aged, Energy Intake, Enteral Nutrition, Female, Humans, Infections, Inflammation, Intensive Care Units, Length of Stay, Male, Middle Aged, Parenteral Nutrition, Prospective Studies, Time Factors, Critical Illness, Practice Guidelines as Topic, Kaplan-Meier Estimate
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