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 the proinflammatory phase of acute trauma or infection, nutrition support may even delay healing due to potential interference with clearance of damage.
“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]
The Discussion says early parenteral nutrition was associated with delayed recovery and speculates that suppressed autophagy could impair clearance of cell damage and microorganisms. That supports the proposed mechanism, but the paper studies critically ill ICU patients receiving early versus late parenteral nutrition; it does not establish the claim for nutrition support generally during a proinflammatory phase of acute trauma or infection. The relevant passage is labeled “Cumulative Proportion” in our copy, without a page number. (LLM, conf=0.86)
Experimental — accuracy not yet measuredLate, 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.
“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]
The Discussion and Secondary Outcomes sections report shorter ICU and hospital stays, fewer infections, and shorter durations of mechanical ventilation and renal-replacement therapy with late PN. But the Discussion explicitly finds no significant mortality difference, and Table 2 shows no meaningful difference in the proportion requiring renal-replacement therapy (8.6% versus 8.9%). The claim overstates both lower mortality and less need for renal support. (LLM, conf=0.92)
Experimental — accuracy not yet measuredEarly supplemental or exclusive PN is associated with increased morbidity including prolonged ICU dependency and mechanical ventilation, increased infection rate, and need for renal replacement therapy.
“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]
The Discussion and Table 2 report longer ICU stays, more infections, and more prolonged mechanical ventilation with early than late parenteral nutrition. Table 2 also shows a longer duration of renal-replacement therapy with early PN, but not an increased need for it: 8.9% versus 8.6% required therapy (P=0.77). (LLM, conf=0.90)
Experimental — accuracy not yet measuredIn 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.
“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]
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredCasaer et al. 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.
“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]
The Discussion reports that late PN was associated with fewer ICU infections and shorter ICU stays, mechanical ventilation, and renal-replacement therapy than early PN. However, Table 2 (Study Intervention) shows no meaningful difference in the proportion requiring renal-replacement therapy (8.9% early vs. 8.6% late; P=0.77). The claim is supported for longer therapy, not increased need for it. (LLM, conf=0.90)
Experimental — accuracy not yet measured
In a sub-group analysis of the EPaNIC study, 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.
“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]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredAdding parenteral nutrition to enteral nutrition to increase intakes was associated with longer ICU stays and higher infection rates.
“Adding parenteral nutrition to enteral nutrition to increase intakes was associated with longer ICU stays and higher infection rates.13,14”
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.
“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”
Toleration of a nutritional deficit during the first week of critical illness results in fewer complications and accelerated recovery.
“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]
In our trial, ICU-acquired infections were less common than in EpaNIC despite greater critical illness severity and higher mortality of patients.
“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.”
In previous randomised trials, nutritional interventions affected time to readiness for ICU discharge but not mortality.
“In previous randomised trials, nutritional interventions affected time to readiness for ICU discharge but not mortality.13,14”
A similar strategy regarding the time to readiness for ICU discharge endpoint has been used previously in studies on nutrition in the ICU.
“A similar strategy regarding this endpoint has been used previously in studies on nutrition in the ICU.13,14”
Results of the Casaer et al. study revealed the potential harm of nutritional intervention aiming at full, possibly overestimated calorie targets during the acute phase of critical illness.
“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]
The EPaniC study including more than 1000 septic patients reached similar conclusions.
“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]
One study showed possible benefit of a further delay of PN if EN is not possible/tolerated in non-malnourished ICU patients.
“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]
One study showed possible benefit of a further delay of PN if EN is not possible or tolerated.
“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]
Results of the EPaNIC study revealed the potential harm of nutritional intervention aiming at full, possibly overestimated calorie targets during the acute phase of critical illness.
“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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Severe Sepsis and Septic Shock
Angus, D. C., & van der Poll, T. (2013) · New England Journal of Medicine · doi:10.1056/nejmra1208623 · Cited by 3,993 · see citing works
Surviving Sepsis Campaign: International guidelines for management of sepsis and septic shock: 2016.
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ESPEN guideline on clinical nutrition in the intensive care unit.
Singer, P., Blaser, A. R., Berger, M. M., Alhazzani, W., Calder, P. C., Casaer, M. P., Hiesmayr, M., Mayer, K., Montejo, J. C., Pichard, C., et al. (2019) · Clinical Nutrition · doi:10.1016/j.clnu.2018.08.037 · Cited by 2,904 · see citing works
“01) with no difference in any mortality outcomes, whereas all these patients received virtually no EN during the seven study days [16].”
BackgroundResultInfluentialSelf-citationESPEN guideline: Clinical nutrition in surgery.
Weimann, A., Braga, M., Carli, F., Higashiguchi, T., Hübner, M., Kłęk, S., Laviano, A., Ljungqvist, O., Lobo, D., Martindale, R., et al. (2017) · Clinical Nutrition · doi:10.1016/j.clnu.2017.02.013 · Cited by 1,665 · see citing works
“Two recent large-scalemulticentre studies investigatedwhether PN should be supplemented “early” (within 4 days) or “late” (after 7 days) in the event of impaired enteral tolerance [246,247] (both 1þþ).”
BackgroundAcute respiratory distress syndrome
Thompson, B. T., Chambers, R. C., & Liu, K. D. (2017) · New England Journal of Medicine · doi:10.1056/nejmra1608077 · Cited by 1,807 · see citing works
Alhazzani, W. A., Møller, M. H., Arabi, Y. M., Loeb, M. B., Gong, M. N., Fan, E., Oczkowski, S. J. W., Levy, M. M., Derde, L. P. G., Dzierba, A. L., et al. (2020) · Critical Care Medicine · doi:10.1097/ccm.0000000000004363 · Cited by 1,567 · see citing works
Taylor, B. E., McClave, S. A., Martindale, R. G., Warren, M. M., Johnson, D. R., Braunschweig, C., McCarthy, M. S., Davanos, E., Rice, T. W., Cresci, G. A., et al. (2016) · Critical Care Medicine · doi:10.1097/ccm.0000000000001525 · Cited by 1,476 · see citing works
Hypoalbuminemia: Pathogenesis and Clinical Significance
Soeters, P. B., Wolfe, R. R., & Shenkin, A. (2019) · Journal of Parenteral and Enteral Nutrition · doi:10.1002/jpen.1451 · Cited by 1,448 · see citing works
Sepsis: pathophysiology and clinical management
Gotts, J. E., & Matthay, M. A. (2016) · BMJ · doi:10.1136/bmj.i1585 · Cited by 1,269 · see citing works
Weiss, S. L., Peters, M. J., Alhazzani, W. A., Agus, M. S. D., Flori, H. R., Inwald, D. P., Nadel, S., Schlapbach, L. J., Tasker, R. C., Argent, A. C., et al. (2020) · Pediatric Critical Care Medicine · doi:10.1097/pcc.0000000000002198 · Cited by 1,268 · see citing works
EASL Clinical Practical Guidelines on the management of acute (fulminant) liver failure
Wendon, J. A., Córdoba, J., Dhawan, A. K., Larsen, F. S., Manns, M. P., Nevens, F., Samuel, D., Simpson, K. J., Yaron, I., & Bernardi, M. (2017) · Journal of Hepatology · doi:10.1016/j.jhep.2016.12.003 · Cited by 1,043 · see citing works
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KDOQI US Commentary on the 2012 KDIGO Clinical Practice Guideline for Acute Kidney Injury
Palevsky, P. M., Liu, K. D., Brophy, P. D., Chawla, L. S., Parikh, C. R., Thakar, C. V., Tolwani, A., Waikar, S. S., & Weisbord, S. D. (2013) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2013.02.349 · Cited by 1,186 · see citing works
Schuetz, P., Fehr, R., Baechli, V., Geiser, M., Deiss, M., Gomes, F., Kutz, A., Tribolet, P., Bregenzer, T., Braun, N., et al. (2019) · The Lancet · doi:10.1016/s0140-6736(18)32776-4 · Cited by 910 · see citing works
ESPEN practical and partially revised guideline: Clinical nutrition in the intensive care unit
Singer, P., Blaser, A. R., Berger, M. M., Calder, P. C., Casaer, M., Hiesmayr, M., Mayer, K., Montejo-Gonzalez, J. C., Pichard, C., Preiser, J.-C., et al. (2023) · Clinical Nutrition · doi:10.1016/j.clnu.2023.07.011 · Cited by 793 · see citing works
“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.”
BackgroundInfluentialSelf-citationHeidegger, C. P., Berger, M. M., Graf, S., Zingg, W., Darmon, P., Costanza, M. C., Thibault, R., & Pichard, C. (2013) · The Lancet · doi:10.1016/s0140-6736(12)61351-8 · Cited by 776 · see citing works
Stress hyperglycemia: an essential survival response!
Marik, P. E., & Bellomo, R. (2013) · Critical Care · doi:10.1186/cc12514 · Cited by 731 · see citing works
Vanhorebeek, I., Latronico, N., & den Berghe, G. V. (2020) · Intensive Care Medicine · doi:10.1007/s00134-020-05944-4 · Cited by 768 · see citing works
“Harm evoked by early parenteral nutrition comprised more ICU-acquired weakness and impaired recovery thereof, longer dependency on mechanical ventilation and a longer stay in the ICU [20, 28, 95].”
BackgroundMethodInfluentialCompher, C., Bingham, A. L., McCall, M., Patel, J., Rice, T. W., Braunschweig, C., & McKeever, L. (2022) · Journal of Parenteral and Enteral Nutrition · doi:10.1002/jpen.2267 · Cited by 747 · see citing works
Blaser, A. R., Malbrain, M. L. N. G., Starkopf, J., Fruhwald, S. M., Jakob, S. M., Waele, J. J. D., Braun, J.-P., Poeze, M., & Spies, C. (2012) · Intensive Care Medicine · doi:10.1007/s00134-011-2459-y · Cited by 651 · see citing works
Permissive underfeeding or standard enteral feeding in critically ill adults
Arabi, Y. M., Aldawood, A. S., Haddad, S. H., Al-Dorzi, H. M., Tamim, H. M., Jones, G., Mehta, S., McIntyre, L., Solaiman, O., Sakkijha, M. H., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1502826 · Cited by 614 · see citing works
Trial of the Route of Early Nutritional Support in Critically Ill Adults
Harvey, S. E., Parrott, F., Harrison, D. A., Bear, D. E., Segaran, E., Beale, R., Bellingan, G., Leonard, R., Mythen, M. G., & Rowan, K. M. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1409860 · Cited by 618 · see citing works
Weiss, S. L., Peters, M. J., Alhazzani, W. A., Agus, M. S. D., Flori, H. R., Inwald, D. P., Nadel, S., Schlapbach, L. J., Tasker, R. C., Argent, A. C., et al. (2020) · Intensive Care Medicine · doi:10.1007/s00134-019-05878-6 · Cited by 638 · see citing works
Reignier, J., Boisramé-Helms, J., Brisard, L., Lascarrou, J.-B., Ait Hssain, A., Anguel, N., Argaud, L., Asehnoune, K., Asfar, P., Bellec, F., et al. (2018) · The Lancet · doi:10.1016/s0140-6736(17)32146-3 · Cited by 595 · see citing works
Early versus late parenteral nutrition in critically ill children
Fivez, T., Kerklaan, D., Mesotten, D., Verbruggen, S., Wouters, P. J., Vanhorebeek, I., Debaveye, Y., Vlasselaers, D., Desmet, L., Casaer, M. P., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1514762 · Cited by 558 · see citing works
Self-citationJacobi, J., Bircher, N. G., Krinsley, J. S., Agus, M. S. D., Braithwaite, S. S., Deutschman, C. S., Freire, A. X., Geehan, D., Kohl, B., Nasraway, S. A., et al. (2012) · Critical Care Medicine · doi:10.1097/ccm.0b013e3182653269 · Cited by 570 · see citing works
Gupta, S., Wang, W., Hayek, S. S., Chan, L., Mathews, K. S., Melamed, M. L., Brenner, S. K., Leonberg-Yoo, A., Schenck, E. J., Radbel, J., et al. (2021) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2020.6252 · Cited by 535 · see citing works
Hermans, G., Mechelen, H. V., Clerckx, B., Vanhullebusch, T., Mesotten, D., Wilmer, A. P., Casaer, M. P., Meersseman, P., Debaveye, Y. A., Cromphaut, S. J. V., et al. (2014) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201312-2257oc · Cited by 536 · see citing works
Self-citation36th International Symposium on Intensive Care and Emergency Medicine
Bateman, R. M., Sharpe, M. D., Jagger, J. E., Ellis, C. G., Solé‐Violán, J., López-Rodríguez, M., Herrera‐Ramos, E., Ruiz-Hernández, J. J., Borderías, L., Horcajada, J. P., et al. (2016) · Critical Care · doi:10.1186/s13054-016-1208-6 · Cited by 555 · see citing works
Metabolic response to the stress of critical illness
Preiser, J., Ichaï, C., Orban, J., & Groeneveld, A. B. J. (2014) · British Journal of Anaesthesia · doi:10.1093/bja/aeu187 · Cited by 513 · see citing works
ASPEN Consensus Recommendations for Refeeding Syndrome
da Silva, J. S. V., Seres, D. S., Sabino, K., Adams, S. C., Berdahl, G. J., Citty, S. W., Cober, M. P., Evans, D. C., Greaves, J. R., Gura, K. M., et al. (2020) · Nutrition in Clinical Practice · doi:10.1002/ncp.10474 · Cited by 542 · see citing works
The rise of mitochondria in medicine
Picard, M. A., Wallace, D. C., & Burelle, Y. (2016) · Mitochondrion · doi:10.1016/j.mito.2016.07.003 · Cited by 454 · see citing works
“…ill adult patient who naturally exhibits low energy requirements due to bedrest and physical inactivity, early-onset intravenous feeding (i.e., parenteral nutrition) promotes metabolic oversupply and is consequently associated with greater morbidity than later-onset feeding (Casaer et al., 2011).”
BackgroundThyroid function in critically ill patients
Fliers, E., Bianco, A. C., Langouche, L., & Boelen, A. (2015) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(15)00225-9 · Cited by 441 · see citing works
Strategies to Prevent Ventilator-Associated Pneumonia in Acute Care Hospitals: 2014 Update
Klompas, M., Branson, R. D., Eichenwald, E. C., Greene, L. R., Howell, M. D., Lee, G. M., Magill, S. S., Maragakis, L. L., Priebe, G. P., Speck, K. A., et al. (2014) · Infection Control and Hospital Epidemiology · doi:10.1086/677144 · Cited by 433 · see citing works
“Initiation of parenteral nutrition in critically ill patients within 48 hours of ICU admission is associated with an increased risk of nosocomial infections and mortality compared with initiating parenteral nutrition on or after 8 days.(139) IV.”
Metabolic and nutritional support of critically ill patients: consensus and controversies
Preiser, J.-C., van Zanten, A. R., Berger, M. M., Biolo, G., Casaer, M. P., Doig, G. S., Griffiths, R. D., Heyland, D. K., Hiesmayr, M., Iapichino, G., et al. (2015) · Critical Care · doi:10.1186/s13054-015-0737-8 · Cited by 416 · see citing works
“The role of inflammation in the metabolic response to stress has been recognized for a long time and is currently under increased scrutiny after the results of the trials from Leuven University [6] [7], in which the magnitude of the inflammatory response was attenuated in patients who received intensive insulin therap…”
BackgroundResultInfluentialSelf-citationKlompas, M., Branson, R. D., Cawcutt, K. A., Crist, M. B., Eichenwald, E. C., Greene, L. R., Lee, G. M., Maragakis, L. L., Powell, K. M., Priebe, G. P., et al. (2022) · Infection Control and Hospital Epidemiology · doi:10.1017/ice.2022.88 · Cited by 435 · see citing works
The Sick and the Weak: Neuropathies/Myopathies in the Critically Ill
Friedrich, O., Reid, M. B., den Berghe, G. V., Vanhorebeek, I., Hermans, G., Rich, M. M., & Larsson, L. (2015) · Physiological Reviews · doi:10.1152/physrev.00028.2014 · Cited by 394 · see citing works
“This was confirmed in a recent RCT (300), and this may also explain the delay in recovery observed with early versus late initiation of parenteral nutrition to supplement insufficient enteral nutrition in critically ill patients (107, 109, 300).”
BackgroundMethodSelf-citationHermans, G., Casaer, M. P., Clerckx, B., Güiza, F., Vanhullebusch, T., Derde, S., Meersseman, P., Derese, I., Mesotten, D., Wouters, P. J., et al. (2013) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(13)70183-8 · Cited by 368 · see citing works
Self-citationWeijs, P. J., Looijaard, W. G., Beishuizen, A., Girbes, A. R., & Oudemans-van Straaten, H. M. (2014) · Critical Care · doi:10.1186/s13054-014-0701-z · Cited by 358 · see citing works
“Of note, the increased rate of infections and longer duration of mechanical ventilation and renal replacement therapy found in the EPaNIC trial [1] could partially be explained by a component of overfeeding, because energy needs were not measured but calculated, and rather high energy targets were attained.”
InfluentialEnergy-dense versus routine enteral nutrition in the critically ill
The TARGET Investigators (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1811687 · Cited by 345 · see citing works
Allingstrup, M. J., Kondrup, J., Wiis, J., Claudius, C., Pedersen, U. G., Hein-Rasmussen, R., Bjerregaard, M. R., Steensen, M., Jensen, T. H., Lange, T., et al. (2017) · Intensive Care Medicine · doi:10.1007/s00134-017-4880-3 · Cited by 341 · see citing works
Nutrition in the acute phase of critical illness
Casaer, M. P., & Van den Berghe, G. (2014) · New England Journal of Medicine · doi:10.1056/nejmra1304623 · Cited by 335 · see citing works
Self-citationElke, G., van Zanten, A. R. H., Lemieux, M., McCall, M., Jeejeebhoy, K. N., Kott, M., Jiang, X., Day, A. G., & Heyland, D. K. (2016) · Critical Care · doi:10.1186/s13054-016-1298-1 · Cited by 378 · see citing works
“The results of our meta-analysis may not be applicable to patients with a relative short-term or absolute contraindication for EN where the treatment effect of PN (as compared to standard care or no nutrition) on clinical outcomes may differ, as shown in two recent large RCTs [33, 34].”
ResultNon-Thyroidal Illness in the ICU: A Syndrome with Different Faces
Van den Berghe, G. (2014) · Thyroid® · doi:10.1089/thy.2014.0201 · Cited by 316 · see citing works
“The latter could in part explain the finding of fewer nosocomial infections with tolerating the macronutrient deficit during acute critical illness (34).”
BackgroundRole of Disease and Macronutrient Dose in the Randomized Controlled EPaNIC Trial
Casaer, M. P., Wilmer, A., Hermans, G., Wouters, P. J., Mesotten, D., & Van den Berghe, G. (2013) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201206-0999oc · Cited by 307 · see citing works
Self-citationACG Clinical Guideline: Nutrition Therapy in the Adult Hospitalized Patient
McClave, S. A., DiBaise, J. K., Mullin, G. E., & Martindale, R. G. (2016) · The American Journal of Gastroenterology · doi:10.1038/ajg.2016.28 · Cited by 283 · see citing works
Dhaliwal, R., Cahill, N., Lemieux, M., & Heyland, D. K. (2014) · Nutrition in Clinical Practice · doi:10.1177/0884533613510948 · Cited by 282 · see citing works
Indirect calorimetry in nutritional therapy. A position paper by the ICALIC study group
Oshima, T., Berger, M. M., De Waele, E., Guttormsen, A. B., Heidegger, C.-P., Hiesmayr, M., Singer, P., Wernerman, J., & Pichard, C. (2017) · Clinical Nutrition · doi:10.1016/j.clnu.2016.06.010 · Cited by 283 · see citing works
Compher, C., Chittams, J., Sammarco, T., Nicolo, M., & Heyland, D. K. (2017) · Critical Care Medicine · doi:10.1097/ccm.0000000000002083 · Cited by 264 · see citing works
Reignier, J., Plantefeve, G., Mira, J.-P., Argaud, L., Asfar, P., Aissaoui, N., Badie, J., Botoc, N.-V., Brisard, L., Bui, H.-N., et al. (2023) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(23)00092-9 · Cited by 270 · see citing works
The evolutionary significance of depression in Pathogen Host Defense (PATHOS-D)
Raison, C. L., & Miller, A. H. (2013) · Molecular Psychiatry · doi:10.1038/mp.2012.2 · Cited by 253 · see citing works
Acute liver failure: A curable disease by 2024?
Bernal, W. E., Lee, W. M., Wendon, J. A., Larsen, F. S., & Williams, R. L. (2015) · Journal of Hepatology · doi:10.1016/j.jhep.2014.12.016 · Cited by 257 · see citing works
“If enteral nutrition is not tolerated later introduction of intravenous feeding may be considered [46].”
BackgroundESPGHAN/ESPEN/ESPR/CSPEN guidelines on pediatric parenteral nutrition: Energy
Joosten, K., Embleton, N., Yan, W., Senterre, T., Braegger, C., Bronský, J., Cai, W., Campoy, C., Carnielli, V. P., Darmaun, D., et al. (2018) · Clinical Nutrition · doi:10.1016/j.clnu.2018.06.944 · Cited by 242 · see citing works
Self-citationESPEN guideline on clinical nutrition in hospitalized patients with acute or chronic kidney disease
Fiaccadori, E., Sabatino, A., Barazzoni, R., Carrero, J. J., Cupisti, A., De Waele, E., Jonckheer, J., Singer, P., & Cuerda, C. (2021) · Clinical Nutrition · doi:10.1016/j.clnu.2021.01.028 · Cited by 277 · see citing works
“Besides, one study in non-malnourished critically-ill patients with AKI described potential advantages in delaying PN if EN is not possible/ tolerated [58,59].”
BackgroundWhen Is Parenteral Nutrition Appropriate?
Worthington, P. H., Balint, J. P., Bechtold, M. L., Bingham, A. L., Chan, L., Durfee, S. M., Jevenn, A., Malone, A. M., Mascarenhas, M. R., Robinson, D. T., et al. (2017) · Journal of Parenteral and Enteral Nutrition · doi:10.1177/0148607117695251 · Cited by 235 · see citing works
Elke, G., Wang, M., Weiler, N., Day, A. G., & Heyland, D. K. (2014) · Critical Care · doi:10.1186/cc13720 · Cited by 232 · see citing works
Egi, M., Ogura, H., Yatabe, T., Atagi, K., Inoue, S., Iba, T., Kakihana, Y., Kawasaki, T., Kushimoto, S., Kuroda, Y., et al. (2021) · Journal of Intensive Care · doi:10.1186/s40560-021-00555-7 · Cited by 226 · see citing works
Picard, M. A., Jung, B., Liang, F., Azuelos, I., Hussain, S. N. A., Goldberg, P., Godin, R., Danialou, G., Chaturvedi, R. K., Rygiel, K. A., et al. (2012) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201206-0982oc · Cited by 220 · see citing works
Appropriate protein provision in critical illness: a systematic and narrative review
Hoffer, L. J., & Bistrian, B. R. (2012) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.111.032078 · Cited by 222 · see citing works
Umpierrez, G. E., Smiley, D., Hermayer, K., Khan, A., Olson, D. E., Newton, C., Jacobs, S., Rizzo, M., Peng, L., Reyes, D., et al. (2013) · Diabetes Care · doi:10.2337/dc12-1988 · Cited by 222 · see citing works
Personalized mechanical ventilation in acute respiratory distress syndrome
Pelosi, P. P., Ball, L., Barbas, C. S. V., Bellomo, R., Burns, K. E. A., Einav, S., Gattinoni, L., Laffey, J. G., Marini, J. J., Myatra, S. N., et al. (2021) · Critical Care · doi:10.1186/s13054-021-03686-3 · Cited by 225 · see citing works
“for out of hospital cardiac arrest [88], early parenteral or enteral nutrition to achieve early full caloric intake [89]; glutamine therapy to correct glutamine deficiency [90]; fluid bolus resuscitation in septic African children [91].”
BackgroundHeyland, D. K., Dhaliwal, R., Wang, M., & Day, A. G. (2014) · Clinical Nutrition · doi:10.1016/j.clnu.2014.07.008 · Cited by 218 · see citing works
Five-year impact of ICU-acquired neuromuscular complications: a prospective, observational study
Aerde, N. V., Meersseman, P., Debaveye, Y. A., Wilmer, A. P., Gunst, J., Casaer, M. P., Bruyninckx, F., Wouters, P. J., Gosselink, R., den Berghe, G. V., et al. (2020) · Intensive Care Medicine · doi:10.1007/s00134-020-05927-5 · Cited by 214 · see citing works
Self-citationInflammation and nutrition: friend or foe?
Stumpf, F., Keller, B., Gressies, C., & Schuetz, P. (2023) · Nutrients · doi:10.3390/nu15051159 · Cited by 213 · see citing works
“Although it can be challenging in clinical practice, a consistent adaptation of nutritional management during the course of critical illness is crucial [92,108,110,111].”
BackgroundIntensive Nutrition in Acute Lung Injury: A Clinical Trial (INTACT)
Braunschweig, C. A., Sheean, P. M., Peterson, S. J., Gomez Perez, S., Freels, S., Lateef, O., Gurka, D., & Fantuzzi, G. (2015) · Journal of Parenteral and Enteral Nutrition · doi:10.1177/0148607114528541 · Cited by 199 · see citing works
“89 Protein received per day, g 82 (23) 60.”
Metabolic phenotype of skeletal muscle in early critical illness
Puthucheary, Z., Astin, R., McPhail, M. J. W., Saeed, S. M. B., Pasha, Y., Bear, D. E., Constantin, D., Velloso, C. P., Manning, S., Calvert, L. D., et al. (2018) · Thorax · doi:10.1136/thoraxjnl-2017-211073 · Cited by 200 · see citing works
The intensive care medicine research agenda in nutrition and metabolism
Arabi, Y. M., Casaer, M. P., Chapman, M. J., Heyland, D. K., Ichaï, C., Marik, P. E., Martindale, R. G., McClave, S. A., Preiser, J., Reignier, J., et al. (2017) · Intensive Care Medicine · doi:10.1007/s00134-017-4711-6 · Cited by 203 · see citing works
Self-citationRisk factors for intensive care unit-acquired weakness: A systematic review and meta-analysis
Yang, T., Li, Z., Jiang, L., Wang, Y., & Xi, X. (2018) · Acta Neurologica Scandinavica · doi:10.1111/ane.12964 · Cited by 203 · see citing works
An update on non-thyroidal illness syndrome
Fliers, E., & Boelen, A. (2021) · Journal of Endocrinological Investigation · doi:10.1007/s40618-020-01482-4 · Cited by 199 · see citing works
Gastro-Intestinal Failure Trial Group, Blaser, A. R., Poeze, M., Malbrain, M. L. N. G., Björck, M., Straaten, H. M. O., & Starkopf, J. (2013) · Intensive Care Medicine · doi:10.1007/s00134-013-2831-1 · Cited by 196 · see citing works
Strategies to Prevent Ventilator-Associated Pneumonia in Acute Care Hospitals: 2014 Update
Klompas, M., Branson, R. D., Eichenwald, E. C., Greene, L. R., Howell, M. D., Lee, G. M., Magill, S. S., Maragakis, L. L., Priebe, G. P., Speck, K. A., et al. (2014) · Infection Control and Hospital Epidemiology · doi:10.1017/s0899823x00193894 · Cited by 194 · see citing works
“Initiation of parenteral nutrition in critically ill patients within 48 hours of ICU admission is associated with an increased risk of nosocomial infections and mortality compared with initiating parenteral nutrition on or after 8 days.(139)”
Boelens, P. G., Heesakkers, F. F. B. M., Luyer, M. D. P., van Barneveld, K. W. Y., de Hingh, I. H. J. T., Nieuwenhuijzen, G. A. P., Roos, A. N., & Rutten, H. J. T. (2014) · Annals of Surgery · doi:10.1097/sla.0000000000000288 · Cited by 192 · see citing works
NutritionDay ICU: a 7 year worldwide prevalence study of nutrition practice in intensive care
Bendavid, I., Singer, P., Theilla, M., Themessl-Huber, M., Sulz, I., Mouhieddine, M., Schuh, C., Mora, B., & Hiesmayr, M. (2017) · Clinical Nutrition · doi:10.1016/j.clnu.2016.07.012 · Cited by 175 · see citing works
Nutritional Status and Mortality in the Critically Ill*
Mogensen, K. M., Robinson, M. K., Casey, J. D., Gunasekera, N. S., Moromizato, T., Rawn, J. D., & Christopher, K. B. (2015) · Critical Care Medicine · doi:10.1097/ccm.0000000000001306 · Cited by 190 · see citing works
“Late initiation of parenteral nutrition in the critically ill is shown to be associated with a less complicated ICU course (51).”
BackgroundKoekkoek, W. A. C. (., van Setten, C. H. (., Olthof, L. E., Kars, J. C. N. (., & van Zanten, A. R. H. (2019) · Clinical Nutrition · doi:10.1016/j.clnu.2018.02.012 · Cited by 188 · see citing works
Pathophysiology of Critical Illness and Role of Nutrition
Sharma, K., Mogensen, K., & Robinson, M. (2019) · Nutrition in clinical practice · doi:10.1002/ncp.10232 · Cited by 153 · see citing works
Wei, X., Day, A. G., Ouellette-Kuntz, H., & Heyland, D. K. (2015) · Critical Care Medicine · doi:10.1097/ccm.0000000000001000 · Cited by 187 · see citing works
“Gastrointestinal 44 (9) 25 (14) 12 (5) 7 (11)”
ESPEN guideline on clinical nutrition in surgery – Update 2025
Weimann, A., Bezmarević, M., Braga, M., Correia, M. I. T. D., Funk-Debleds, P., Gianotti, L. V., Gillis, C., Hübner, M., Inciong, J. F. B., Jahit, M. S., et al. (2025) · Clinical Nutrition · doi:10.1016/j.clnu.2025.08.029 · Cited by 204 · see citing works
The Relationship Among Obesity, Nutritional Status, and Mortality in the Critically Ill*
Robinson, M., Mogensen, K., Casey, J., McKane, C., Moromizato, T., Rawn, J., & Christopher, K. (2015) · Critical Care Medicine · doi:10.1097/ccm.0000000000000602 · Cited by 156 · see citing works
“Late initiation of PN in the critically ill is shown to be associated with a less complicated ICU course (99).”
BackgroundThe evolutionary benefit of insulin resistance
Soeters, M. R., & Soeters, P. B. (2012) · Clinical Nutrition · doi:10.1016/j.clnu.2012.05.011 · Cited by 176 · see citing works
Liver Injury and Failure in Critical Illness
Horvatits, T., Drolz, A., Trauner, M. A., & Fuhrmann, V. (2019) · Hepatology · doi:10.1002/hep.30824 · Cited by 168 · see citing works
“(16,33) Typical risk factors for new onset of cholestasis are preexisting liver disease, shock, severe respiratory insufficiency, renal failure, as well as total parenteral nutrition.(21,34) Vasopressors decrease bile flow and excretion of BAs possibly through intracellular increase of calcium in hepatocytes.”
BackgroundFlechet, M., Güiza, F., Schetz, M., Wouters, P., Vanhorebeek, I., Derese, I., Gunst, J., Spriet, I., Casaer, M., Van den Berghe, G., et al. (2017) · Intensive Care Medicine · doi:10.1007/s00134-017-4678-3 · Cited by 169 · see citing works
Self-citationManagement of Hyperglycemia During Enteral and Parenteral Nutrition Therapy
Gosmanov, A. R., & Umpierrez, G. E. (2012) · Current Diabetes Reports · doi:10.1007/s11892-012-0335-y · Cited by 165 · see citing works
Derde, S., Vanhorebeek, I., Güiza, F., Derese, I., Gunst, J., Fahrenkrog, B., Martinet, W., Vervenne, H. B. V. K., Ververs, E.-J., Larsson, L., et al. (2012) · Endocrinology · doi:10.1210/en.2011-2068 · Cited by 164 · see citing works
Berlana, D. (2022) · Nutrients · doi:10.3390/nu14214480 · Cited by 165 · see citing works
“However, the timing of the initiation of EN or PN or a combination of both remains controversial [16,154,155].”
BackgroundResultInfluentialHalpern, S. D., Becker, D., Curtis, J. R., Fowler, R., Hyzy, R. C., Kaplan, L. J., Rawat, N., Sessler, C. N., Wunsch, H., & Kahn, J. M. (2014) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201407-1317st · Cited by 164 · see citing works
A guide to enteral nutrition in intensive care units: 10 expert tips for the daily practice
Preiser, J.-C., Arabi, Y. M., Berger, M. M., Casaer, M., McClave, S., Montejo-González, J. C., Peake, S., Reintam Blaser, A., Van den Berghe, G., van Zanten, A., et al. (2021) · Critical Care · doi:10.1186/s13054-021-03847-4 · Cited by 166 · see citing works
“Moreover, some harm can be related to excessive amounts of proteins in a post hoc analysis of prospective trials performed in adults [45, 84, 85] or in children [86] and in a retrospective study [87].”
BackgroundSelf-citationPetros, S., Horbach, M., Seidel, F., & Weidhase, L. (2016) · Journal of Parenteral and Enteral Nutrition · doi:10.1177/0148607114528980 · Cited by 163 · see citing works
“A recent study showed that early initiation of supplemental PN was associated with more nosocomial infections and a longer ICU stay than late initiation, but without any significant difference in mortality.(30) However, other authors came to a different conclusion.”
ResultVanhorebeek, I., Verbruggen, S. C. A. T., Casaer, M. P., Gunst, J., Wouters, P. J., Hanot, J., Guerra, G. G., Vlasselaers, D., Joosten, K., & den Berghe, G. V. (2017) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(17)30186-8 · Cited by 163 · see citing works
Self-citationTight blood-glucose control without early parenteral nutrition in the ICU
Gunst, J., Debaveye, Y., Güiza, F., Dubois, J., De Bruyn, A., Dauwe, D., De Troy, E., Casaer, M. P., De Vlieger, G., Haghedooren, R., et al. (2023) · New England Journal of Medicine · doi:10.1056/nejmoa2304855 · Cited by 163 · see citing works
Self-citationGunst, J., Derese, I., Aertgeerts, A., Ververs, E.-J., Wauters, A., den Berghe, G. V., & Vanhorebeek, I. (2012) · Critical Care Medicine · doi:10.1097/ccm.0b013e3182676657 · Cited by 160 · see citing works
Advantages of enteral nutrition over parenteral nutrition
Seres, D. S., Valcarcel, M., & Guillaume, A. (2013) · Therapeutic Advances in Gastroenterology · doi:10.1177/1756283x12467564 · Cited by 159 · see citing works
Wischmeyer, P. E., Hasselmann, M., Kummerlen, C., Kozar, R., Kutsogiannis, D. J., Karvellas, C. J., Besecker, B., Evans, D. K., Preiser, J.-C., Gramlich, L., et al. (2017) · Critical Care · doi:10.1186/s13054-017-1736-8 · Cited by 153 · see citing works
“This challenge in obtaining functional outcomes post-ICU stay has been observed in similar trials, such as the EPaNIC trial, where only approximately 26% of enrolled patients were able to complete or provide data at the ICU discharge 6minute walk test [10].”
MethodFeeding the Critically Ill Patient
McClave, S. A., Martindale, R. G., Rice, T. W., & Heyland, D. K. (2014) · Critical Care Medicine · doi:10.1097/ccm.0000000000000654 · Cited by 156 · see citing works
“Although the optimal timing remains unclear, adding supplemental PN to hypocaloric EN should be considered in the high-risk patient, at some point after the first few days in the ICU if enteral feeds are providing less than 60% of caloric and protein goal requirements (mimicking the control group who received late PN…”
BackgroundMethodInfluentialLipids in the intensive care unit: Recommendations from the ESPEN Expert Group
Calder, P. C., Adolph, M., Deutz, N. E., Grau, T., Innes, J. K., Klek, S., Lev, S., Mayer, K., Michael-Titus, A. T., Pradelli, L., et al. (2018) · Clinical Nutrition · doi:10.1016/j.clnu.2017.08.032 · Cited by 158 · see citing works
“In terms of the safety of PN compared with EN in critically ill patients, whilst PN is associated with a lower mortality risk, particularly when compared to late EN, it has an increased risk of infectious complications [14,15].”
BackgroundWinning the war against ICU-acquired weakness: new innovations in nutrition and exercise physiology
Wischmeyer, P. E., & San-Millan, I. (2015) · Critical Care · doi:10.1186/cc14724 · Cited by 153 · see citing works
- 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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