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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]
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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.”
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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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“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]
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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 practical and partially revised guideline: Clinical nutrition in the intensive care unit (2023) · cites this paper as [14]
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“These counterintuitive fi ndings, corroborating those from adult ICU studies [30], were attributed to a ‘ fasting response ’ , characterized by increased ketogenesis and endocrine response [7,24,30,31].”
Mastering the brain in critical conditions: an update
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“…in pioneer randomized controlled trials (RCTs) has been attributed to avoiding iatrogenic severe hyperglycemia evoked by early parenteral nutrition [40]; a feeding strategy that was abandoned after RCTs showed harm as compared with withholding parenteral nutrition in the first week in ICU [41, 42].”
BackgroundSelf-citationCritical care: Meeting protein requirements without overfeeding energy
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“However, these studies provided 50% of current protein guidelines, inaccurately estimated energy requirements, risking under- and overfeeding, gave a higher proportion of protein to underfed patients [17], provided excess non-protein energy in the first 48 h [18] or included only well-nourished patients [23], the grou…”
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Mulherin, D. W., & Cogle, S. V. (2017) · Hospital Pharmacy · doi:10.1310/hpj5201-17 · Cited by 18
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Role of ketones, ketogenic diets and intermittent fasting in ICU
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Self-citationRole of Nutrition Support in Inflammatory Conditions
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Feeding During Phases of Altered Mitochondrial Activity: A Theory
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Le concept du « Baby stomach » appliqué à la nutrition du patient agressé
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“[1] Casaer MP, Mesotten D, Hermans G, Wouters PJ, Schetz M, Meyfroidt G, et al.”
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“However, the Leuven studies were conducted in the context of early supplementation of insufficient enteral nutrition by intravenous glucose and parenteral nutrition (PN), which may have exacerbated hyperglycemia to more harmful levels in the control group [8, 9].”
Combined Effects of Early Mobilization and Nutrition on ICU-Acquired Weakness
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“For instance, a randomized multi-center trial by Caesar et al. [75] found that delaying parenteral nutrition led to faster recovery and fewer complications, suggesting that the benefits of early full nutritional support may not always be universally applicable and might even cause harm in some…”
Early versus late Parenteral Nutrition in Critically Ill Adults
Daly, J. M. (2012) · Yearbook of Surgery · doi:10.1016/j.ysur.2012.03.050 · Cited by 17
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Impact of early nutrition and feeding route on clinical outcomes of neurocritically ill patients
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“EPN may be associated with delayed recovery and more complications, as compared with late parenteral nutrition [21].”
Parenteral Nutrition: Current Use, Complications, and Nutrition Delivery in Critically Ill Patients
Delgado, J. C. L., Carmona, T. G., Marco, E. M., Bordeje-Laguna, M. L., Portugal-Rodríguez, E., Lorencio, C., Vera, P., Redín, L. M., Llorente-Ruiz, B., Iglesias-Rodriguez, R., et al. (2023) · Nutrients · doi:10.3390/nu15214665 · Cited by 21
“Contemporary studies reported a mean protein delivery of between 0.8 and 1.1 g · Kg − 1 · day − 1 [20–23], and a recent prospective multinational cohort study in patients with ICU stays ≥ 5 days found that their protein intake did not achieve current recommendations (i.e., 1.2–1.3 g · Kg − 1 · day…”
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Management of acute pancreatitis (AP) – Polish Pancreatic Club recommendations
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“Parenteral nutrition can be considered in case of very poor tolerance of enteral feeding, preventing an adequate energy supply, or extended persistence of paralytic ileus [37].”
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“Moreover, more infections and worse muscle weakness were observed in patients with early supplemental parenteral nutrition [21,22].”
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“Copyright © 2022 American Associa the first week rarely meet energy and protein requirements because of the frequent pausing of feedings for interventions and procedures early in the hospitalization and/or feeding intolerance, routinely providing less than 50% of caloric and protein needs.(5,6) Furthermore, when energ…”
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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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