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- Guideline Nutritional support for critically ill patients by the Korean Society for Parenteral and Enteral Nutrition—part II: a clinical practice guideline
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Jae Gil Lee1
, You Min Sohn2, Seung Hwan Lee3, Yun Tae Jung4, Hak-Jae Lee5, Jeong Yun Park6, Nak-Jun Choi7, Jung Mi Song, RN, MSN8, Jee Young Lee9, Ji Yeon Kim10, Ji Yeong Jeong11, Ye Won Sung12, Eun Jeong Park12, Hyun Ji Ko13, Ji Yoon Cho14, Bomi Kim15, Yesung Oh16, In Chung Lee17, Jin Young Lee18,19, A Ram Kim20, Jee Yeon Lee21, Seong-Eun Kim22, Tae Sun Ha23, Min Kwan Kwon24 -
Annals of Clinical Nutrition and Metabolism 2026;18(2):65-116.
DOI: https://doi.org/10.15747/ACNM.26.0059
Published online: July 31, 2026
1Department of Surgery, Ewha Womans University College of Medicine, Ewha Womans University Mokdong Hospital, Seoul, Korea
2Department of Pharmacy, Samsung Medical Center, Seoul, Korea
3Department of Trauma Surgery, Gachon University College of Medicine, Gachon University Gil Medical Center, Incheon, Korea
4Department of Surgery, Gangneung Asan Hospital, Gangneung, Korea
5Department of Surgery, Uijeongbu Eulji Medical Center, Eulji University, Uijeongbu, Korea
6Department of Clinical Nursing, University of Ulsan, Seoul, Korea
7Department of Surgery, Korea University Guro Hospital, Seoul, Korea
8Department of Nursing, Asan Medical Center, Seoul, Korea
9Department of Nursing, Kosin University Gospel Hospital, Busan, Korea
10Department of Clinical Nutrition, National Cancer Center, Goyang, Korea
11Department of Clinical Nutrition, Ewha Womans University College of Medicine, Ewha Womans University Mokdong Hospital, Seoul, Korea
12Department of Pharmacy, Chungnam National University Hospital, Daejeon, Korea
13Department of Clinical Nutrition, Gachon University Gil Medical Center, Incheon, Korea
14Department of Pharmacy, Daegu Fatima Hospital, Daegu, Korea
15Department of Pharmacy, Seoul National University Hospital, Seoul, Korea
16Department of Clinical Nutrition, Ajou University Hospital, Suwon, Korea
17Department of Nursing, Gachon University Gil Medical Center, Incheon, Korea
18Department of Surgery, Korea University Guro Hospital, Seoul, Korea
19Trauma Center, Armed Forces Capital Hospital, Seongnam, Korea
20Department of Nutrition Services, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
21Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
22Department of Internal Medicine, Ewha Womans University College of Medicine, Ewha Womans University Mokdong Hospital, Seoul, Korea
23Department of Surgery, Soonchunhyang University College of Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
24Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Korea
- Corresponding author: Jae Gil Lee, email: jakii71@gmail.com
• Received: June 11, 2026 • Revised: July 6, 2026 • Accepted: July 6, 2026
© 2026 The Korean Society of Surgical Metabolism and Nutrition · The Korean Society for Parenteral and Enteral Nutrition · Asian Society of Surgical Metabolism and Nutrition
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Abstract
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Purpose Nutritional therapy is an essential component of intensive care management. Appropriate nutritional support may reduce infectious and metabolic complications and promote recovery in critically ill patients. However, nutritional practices vary across institutions, and international guidelines may not be directly applicable to clinical practice in Korea. Evidence-based clinical practice guidelines that reflect Korean intensive care unit practice are therefore needed.
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Methods The Korean Society for Parenteral and Enteral Nutrition developed these clinical practice guidelines for nutritional therapy in critically ill adults through a systematic literature review and multidisciplinary expert consensus.
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Results In total, 24 key clinical questions and 59 recommendations were developed. The guidelines address enteral and parenteral nutrition, feeding intolerance, aspiration prevention, energy and protein assessment, immune-modulating nutrition, micronutrient supplementation, refeeding syndrome, and disease-specific nutritional therapy for critically ill adults, including those with acute kidney injury, acute liver failure, acute respiratory distress syndrome, sepsis, trauma, and obesity. The recommendations emphasize individualized nutritional therapy according to hemodynamic status, metabolic phase, organ dysfunction, nutritional risk, and treatment goals.
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Conclusion These guidelines provide practical, evidence-based recommendations for nutritional therapy in critically ill adults and reflect both current international evidence and Korean clinical practice. They may support more standardized and consistent nutritional support in Korean intensive care units.
Introduction
Critically ill adult patients are at high risk of malnutrition because severe illness, inflammation, weight loss, and inadequate nutritional intake commonly coexist during intensive care unit treatment. Malnutrition in intensive care unit patients is closely associated with adverse clinical outcomes, including increased infections, delayed recovery, longer hospital stays, and higher mortality [1-7].
In critically ill patients, acute inflammation and stress responses markedly alter normal energy and protein metabolism. Increased endogenous energy production and oxidative stress are common during this phase. These metabolic changes make the timing, amount, and composition of nutritional therapy clinically important. Therefore, nutritional support in the intensive care unit should not be viewed simply as calorie replacement, but as part of active treatment for critically ill patients. Appropriate nutritional therapy may support recovery and improve survival [8-12]. For this reason, this guideline uses the term medical nutrition therapy rather than nutritional support alone.
Many critically ill patients cannot maintain normal oral intake because of mechanical ventilation, impaired consciousness, or organ failure. Individualized nutritional strategies using enteral nutrition or parenteral nutrition (PN) are therefore often necessary [13,14]. Nutritional therapy in the intensive care unit also requires a multidisciplinary approach involving physicians, nurses, pharmacists, and dietitians. Close collaboration among healthcare professionals and standardized clinical guidelines is important for effective nutritional management [15-17].
In 2024, the Korean Society for Parenteral and Enteral Nutrition (KSPEN) published the first evidence-based Korean clinical practice guideline for nutritional support in critically ill adults, Part I, which addressed seven key clinical questions commonly encountered in intensive care unit practice [18]. That guideline provided a practical framework suited to the Korean medical environment and served as an initial step toward standardized nutritional care for critically ill patients. However, Part I covered only seven core topics and could not fully address the broad range of clinical situations encountered in daily intensive care unit practice. Therefore, the current guideline, Part II, was developed to expand the previous guideline by adding 24 key clinical questions related to nutritional therapy in critically ill adults.
In this guideline, early nutritional therapy does not refer to a strict time cutoff. Instead, it refers to starting nutritional therapy without unnecessary delay during the early phase of critical illness while considering the patient’s metabolic condition and clinical stability. Based on this concept, previous international guidelines have generally recommended starting nutritional therapy relatively early after intensive care unit admission, usually within 24–48 hours when feasible.
This guideline was developed using current evidence and expert consensus to improve the practical use and clinical applicability of nutritional therapy in critically ill adults. These recommendations are intended to help clinicians make more consistent, evidence-based decisions across diverse clinical situations and to improve patient outcomes and the quality of nutritional therapy in Korea.
Methods
These clinical practice guidelines were developed through collaboration among multidisciplinary healthcare professionals involved in nutritional therapy for critically ill patients, including physicians, nurses, pharmacists, and dietitians, together with experts in guideline development methodology. The purpose of these guidelines is to provide evidence-based recommendations for nutritional therapy in critically ill adults based on current evidence and expert consensus and to support healthcare professionals in making effective, consistent clinical decisions. In addition, these guidelines were designed to reflect the real-world practice environment of Korean intensive care units while incorporating current international recommendations and standards. They aim to provide standardized, practical recommendations for nutritional therapy in critically ill adults in Korea. Ultimately, these guidelines aim to improve the quality and consistency of nutritional therapy and contribute to better patient outcomes and public health.
These guidelines are intended for healthcare professionals involved in nutritional therapy for critically ill patients, including intensivists, surgeons, physicians, nurses, pharmacists, and dietitians. The target population includes critically ill adults aged 18 years or older who are admitted to the intensive care unit. The scope of these guidelines covers key components of nutritional therapy, including selection of the nutritional route, timing of nutrition initiation, assessment of energy requirements, and evaluation of nutrient composition and requirements. In addition to general critical illness, these guidelines address nutritional therapy strategies for specific disease conditions, including acute respiratory distress syndrome (ARDS), acute kidney injury (AKI), acute liver failure, sepsis, and trauma. These guidelines do not address nutritional therapy in pediatric or neonatal critically ill patients.
These guidelines were developed to reflect the current practice environment for nutritional therapy in Korean intensive care units and to provide evidence-based recommendations applicable to real clinical settings. However, several limitations should be acknowledged. First, because of the limited number of domestic studies, most evidence used in these guidelines was derived from international studies. For several key clinical questions, high-quality randomized controlled trials (RCTs) were limited. For selected key clinical questions with limited RCT evidence or substantial heterogeneity, recommendations were based on narrative evidence synthesis and expert consensus. Therefore, the certainty of evidence supporting some recommendations may be relatively low. Second, because high-quality studies involving Korean patients, especially RCTs, were limited, it was difficult to fully reflect the characteristics of the Korean population and clinical practice environment. Further clinical studies and evidence generation involving Korean critically ill patients are needed. Third, because these guidelines address a broad range of nutritional issues in critically ill adults, the amount and quality of evidence varied substantially across key clinical questions. Accordingly, some recommendations were based primarily on expert consensus and clinical applicability rather than high-certainty evidence. Despite these limitations, the current guideline expands the previous Part I guideline and covers a broader range of topics comparable to those addressed in international guidelines, such as those from the European Society for Clinical Nutrition and Metabolism (ESPEN) and the American Society for Parenteral and Enteral Nutrition (ASPEN). Future updates, supported by additional domestic research and regular revision, may further improve the quality and applicability of these Korean evidence-based clinical practice guidelines.
These guidelines were developed by the Guideline Committee of KSPEN through multidisciplinary collaboration among physicians, nurses, pharmacists, dietitians, and methodology experts. The composition and roles of the guideline development group are summarized on the title page. The guideline development process included key question (KQ) formulation, literature review, evidence appraisal, recommendation drafting, and expert consensus. Regular meetings were held throughout the development process to review the evidence, discuss clinical applicability, and finalize recommendation statements.
These guidelines were developed using an evidence-based approach combined with expert consensus to standardize nutritional therapy in critically ill adults [19]. The guideline development process followed the Appraisal of Guidelines for Research and Evaluation (AGREE) reporting framework. The overall development process consisted of three stages: (1) planning, (2) guideline development, and (3) external review and dissemination. The guideline development process included the following steps: (1) selection of KQs, (2) literature search and study selection, (3) evidence appraisal and synthesis, (4) determination of the certainty of evidence and strength of recommendations, (5) drafting of recommendations, and (6) consensus development. Depending on the amount and quality of evidence, either systematic review/meta-analysis or narrative review methods were applied to each KQ.
Selection of KQs
KQs were developed based on existing international guidelines, including those from ESPEN and ASPEN, with a focus on clinically important or debated issues related to nutritional therapy in critically ill adults. Candidate topics were selected by considering evidence availability, clinical applicability, and relevance to Korean intensive care unit practice. Through committee discussion, 24 key clinical questions were finalized using the PICO (Population, Intervention, Comparison, and Outcome) format, comprising population, intervention, comparator, and outcome.
Development methodology
These guidelines were developed using a mixed approach that combined adaptation and partial de novo development. Existing international guidelines were reviewed and adapted to reflect Korean intensive care unit practice patterns and the local healthcare environment. For selected KQs with sufficient RCT evidence, systematic reviews and meta-analyses were performed. For questions with limited RCT evidence or substantial heterogeneity among studies, narrative review and narrative synthesis approaches were applied.
Literature search and study selection
Literature searches were conducted in PubMed, Embase, the Cochrane Library, and KoreaMed. In principle, studies published after January 1, 2010, were included, although the search period varied according to the characteristics of each KQ. For questions with sufficient RCT evidence, systematic reviews and meta-analyses were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement. Two reviewers independently screened studies and assessed eligibility according to predefined inclusion and exclusion criteria. Disagreements were resolved through discussion or consultation with a third reviewer. For questions with limited RCT evidence or substantial heterogeneity, evidence was summarized using a narrative review approach. Detailed search strategies and PRISMA flow diagrams for each KQ are presented in the supplementary materials.
Risk of bias assessment and evidence synthesis
For questions involving systematic reviews and meta-analyses, risk of bias assessment was performed using the Cochrane Risk of Bias 1.0 tool. Meta-analyses were conducted using Review Manager software (RevMan version 5.4), and random-effects models were applied when substantial heterogeneity was identified. For questions for which quantitative synthesis was not feasible, evidence was synthesized narratively based on clinically relevant findings.
Determination of the level of evidence and strength of recommendations
The certainty of evidence and strength of recommendations were determined according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology (Table 1, Fig. 1). The certainty of evidence was classified as high, moderate, low, or very low. GRADEpro (McMaster University, Canada) was used for evidence profiling and Summary of Findings (SoF) tables. SoF tables were prepared only for questions supported by RCTs or systematic reviews. For narrative review-based questions, recommendations were presented as expert consensus statements. The wording of recommendations followed GRADE guidance according to recommendation strength. Recommendation strength and corresponding wording are summarized in Table 2.
Development of recommendations and consensus process
Draft recommendations were prepared by guideline committee members assigned to each KQ. The recommendations included recommendation statements, evidence summaries, references, recommendation strength, and certainty of evidence. Consensus was achieved through structured multidisciplinary discussion and anonymous voting involving KSPEN executive board members and guideline development committee members. Recommendations with ≥75% agreement were accepted. Agreement rates were categorized into four levels according to the percentage of agreement votes (Table 3).
Independent external review
The draft guidelines underwent independent external review by experts from related academic societies involved in critical care and nutritional therapy, including the Korean Society of Critical Care Medicine, Korean Society of Acute Care Surgery, and Korean Association of Critical Care Nurses. Reviewer comments regarding scientific validity, clinical applicability, and clarity of recommendations were reviewed by the guideline committee and incorporated into the final guideline when appropriate. External reviewers did not participate in final voting.
Funding and editorial independence
These guidelines were developed with support from KSPEN and did not receive commercial or external funding. Administrative support from the society had no influence on topic selection, evidence evaluation, recommendation formulation, or any academic decision-making process. All recommendations were developed through the independent judgment of the guideline committee.
Methodological and technical support
Literature searches were conducted with support from the Medical Library of Asan Medical Center. Methodological consultation regarding guideline development was provided by the National Evidence-based Healthcare Collaborating Agency (NECA). This support was limited to technical and methodological consultation and did not influence the final recommendations.
Management of conflicts of interest
All guideline development committee members declared no financial or nonfinancial conflicts of interest related to these guidelines. Potential conflicts of interest were reviewed before recommendation finalization.
Guideline updating plan
These guidelines expand the previous 2024 Part I guideline by incorporating additional KQs covering broader aspects of nutritional therapy in critically ill adults. Regular revision is planned approximately every 5 years or earlier if important new evidence emerges.
Dissemination and implementation plan
These guidelines will be disseminated through academic meetings and educational activities organized by KSPEN. A summarized practical version of the guideline will also be developed to facilitate implementation in routine clinical practice. In addition, summary tables and practical algorithms will be provided to facilitate bedside implementation. The main contents of the guideline will also be incorporated into educational programs and academic activities to promote the application of evidence-based nutritional therapy in critically ill adults.
Results
In total, 24 key clinical questions and 59 recommendations were developed and organized into thematic categories. Detailed recommendations and supporting evidence are presented in the following sections, and a summary of recommendations is provided in Table 4. Detailed search strategies, evidence tables, study summaries, meta-analyses, and supplementary figures for each KQ are provided in the supplementary materials.
KQ 1. Who should be considered for nutrition therapy in critically ill adult patients?
R1. Critically ill adult patients expected to stay in the intensive care unit for more than 48 hours are considered at risk for malnutrition, and nutrition therapy is suggested. (Expert consensus, strong consensus: 95%)
Critically ill patients may rapidly develop muscle wasting and malnutrition because systemic inflammation and metabolic alterations begin early after intensive care unit admission [20,21]. In a prospective observational study, Puthucheary et al. [21] demonstrated a significant reduction in rectus femoris muscle area shortly after intensive care unit admission, particularly in patients with multiorgan failure. A meta-analysis by Fazzini et al. [22] also reported significant muscle loss and a high prevalence of intensive care unit-acquired weakness during the first week of critical illness. The ESPEN guideline recommends considering patients expected to stay in the intensive care unit for more than 48 hours to be at nutritional risk [20]. Heyland et al. [23] reported that adequate energy and protein delivery was associated with reduced mortality in patients with a Nutrition Risk in the Critically Ill (NUTRIC) score ≥5. However, a meta-analysis by Chong et al. [24] did not demonstrate a consistent association between increased energy or protein delivery and mortality reduction in patients with malnutrition or nutritional risk. Therefore, patients expected to remain in the intensive care unit for more than 48 hours should be considered at high risk for malnutrition and as candidates for early nutritional therapy (Supplement Tables 1, 2).
KQ 2. How should malnutrition and nutritional risk be screened and assessed in critically ill adult patients?
R2. Screening for malnutrition or nutritional risk using a structured tool is suggested within 24–48 hours after intensive care unit admission. (Expert consensus, strong consensus: 100%)
R3. Use of validated tools such as the modified NUTRIC (mNUTRIC) score or Nutritional Risk Screening 2002 (NRS-2002) is suggested for nutritional risk screening. (Expert consensus, strong consensus: 97%)
R4. Standardized assessment and diagnosis using tools such as the Global Leadership Initiative on Malnutrition (GLIM) criteria or Subjective Global Assessment (SGA) are suggested in patients at risk, followed by appropriate nutrition care planning. (Expert consensus, strong consensus: 100%)
Malnutrition in critically ill patients is associated with increased mortality, infectious complications, prolonged mechanical ventilation, and longer intensive care unit stays [25,26]. Therefore, early screening and assessment of nutritional risk after intensive care unit admission are important [27]. Commonly used nutritional risk screening tools in critically ill patients include the mNUTRIC score, NRS-2002, and the Malnutrition Universal Screening Tool (MUST) [5,28]. Among these, the mNUTRIC score was specifically developed for critically ill patients and has been associated with mortality, duration of mechanical ventilation, and intensive care unit length of stay across diverse intensive care unit populations [29-35]. NRS-2002 is also recommended in international guidelines as a nutritional risk screening tool for hospitalized and critically ill patients [1,5,27]. Institution-specific screening tools that reflect local intensive care unit practice patterns may also be considered in Korea [36-38].
Malnutrition assessment and diagnosis may be performed using the GLIM criteria and SGA [39]. The GLIM criteria provide a structured framework that integrates clinical and pathophysiological factors [40,41], and several studies have reported improved prognostic performance when the GLIM criteria are combined with the mNUTRIC score [42]. SGA has also been associated with malnutrition diagnosis and prognostic prediction in critically ill patients and may be useful in intensive care unit settings where body composition assessment is difficult [43,44].
Individualized nutritional interventions based on structured nutritional screening and assessment are associated with improved nutritional status and better clinical outcomes, including reduced mortality, infectious complications, and functional decline. Therefore, structured nutritional risk screening should be performed early after intensive care unit admission, followed by standardized nutritional assessment and individualized nutritional therapy in high-risk patients (Supplement Table 3).
KQ 3. When should nutritional therapy be initiated in critically ill adult patients?
R5. Early initiation of nutritional therapy as soon as possible after hemodynamic stability has been achieved is suggested. (Expert consensus, strong consensus: 100%)
R6. Enteral nutrition is suggested as the preferred route, and PN may be applied on an individual basis according to the patient’s clinical condition. (Expert consensus, strong consensus: 97%)
Early nutritional therapy is important in critically ill patients to reduce metabolic stress, muscle wasting, and infectious complications. ESPEN, the Society of Critical Care Medicine–American Society for Parenteral and Enteral Nutrition (SCCM-ASPEN), and the European Society of Intensive Care Medicine (ESICM) guidelines recommend initiating early enteral nutrition within 24–48 hours after intensive care unit admission in patients without contraindications to enteral feeding [1,5,20,45-47].
Compared with delayed enteral nutrition or no nutritional therapy, early enteral nutrition has been associated with fewer infectious complications, shorter duration of mechanical ventilation, and shorter intensive care unit stays. A meta-analysis by Moon et al. [48] reported that early enteral nutrition was associated with reduced intensive care unit length of stay in patients with sepsis, whereas a meta-analysis by Talebi et al. [49] demonstrated reductions in infectious complications and mortality.
In contrast, the EPaNIC trial, which evaluated early PN, reported increased infectious complications, prolonged mechanical ventilation, and prolonged renal replacement therapy in the early PN group [50]. Therefore, enteral nutrition should be prioritized whenever feasible, and PN should be considered selectively in patients with contraindications to enteral nutrition or insufficient enteral intake.
Recent studies have also evaluated very early enteral nutrition initiated within 6–24 hours after intensive care unit admission [51-53]. Some studies have suggested associations with reduced intensive care unit length of stay and shorter duration of mechanical ventilation, although the overall level of evidence remains limited because of small study sizes and heterogeneous patient populations.
Overall, initiation of nutritional therapy within 24–48 hours after intensive care unit admission is considered appropriate in critically ill patients. PN should be applied selectively according to the patient’s clinical condition when enteral nutrition is not feasible or is insufficient (Supplement Tables 4, 5).
KQ 4. When should enteral nutrition be delayed or discontinued in critically ill patients?
R7. Initiation of enteral nutrition is not suggested in hemodynamically unstable patients until hemodynamic stability has been achieved. (Expert consensus, strong consensus: 97%)
R8. Initiation of low-dose enteral nutrition (10–20 mL/hr) is suggested in patients receiving vasopressors when adequate hemodynamic stability has been achieved and vasopressor doses are stable or decreasing. (Expert consensus, strong consensus: 100%)
R9. Withholding or discontinuation of enteral nutrition is suggested in the following situations. (Expert consensus, strong consensus: 97%)
• Uncontrolled shock and hypoperfusion: lack of hemodynamic stability, increasing vasopressor requirements, elevated serum lactate levels, or suspected tissue hypoperfusion
• Uncontrolled life-threatening respiratory failure: severe hypoxemia, hypercapnia, or acidosis
• Active gastrointestinal bleeding
• Gastrointestinal dysfunction or severe enteral feeding intolerance (EFI): severe abdominal distension, gastric residual volume (GRV) >500 mL over 6 hours, uncontrolled vomiting with aspiration risk, or severe diarrhea
• High-output intestinal fistula or stoma when safe enteral feeding distal to the fistula or stoma is not feasible
• Structural gastrointestinal injury: unresolved intestinal perforation, mechanical bowel obstruction, or bowel ischemia
• Abdominal compartment syndrome
Evidence from RCTs regarding the optimal timing of enteral nutrition initiation in critically ill patients with shock or vasopressor support is limited, and current evidence is based mainly on observational studies and international guidelines. ESPEN and SCCM-ASPEN guidelines recommend withholding enteral nutrition until adequate hemodynamic stability has been achieved [1,5,20,45,54]. However, several studies and guidelines suggest that low-dose enteral nutrition may be cautiously initiated in patients receiving vasopressors when blood pressure is stable and vasopressor doses are stable or decreasing [1,5,45]. Multiple observational studies have reported that early enteral nutrition during vasopressor therapy was associated with reduced mortality, shorter duration of mechanical ventilation, and decreased intensive care unit length of stay [55-60]. Better enteral feeding tolerance has also been reported in patients receiving lower norepinephrine-equivalent doses. In contrast, elevated serum lactate levels, high-dose vasopressor requirements, tissue hypoperfusion, or suspected bowel ischemia may increase the risk of enteral nutrition-related complications [45,54,61]. In addition, uncontrolled severe respiratory failure, active gastrointestinal bleeding, bowel ischemia, intestinal perforation, mechanical bowel obstruction, abdominal compartment syndrome, and severe gastrointestinal intolerance are recognized situations requiring withholding or discontinuation of enteral nutrition [1,5,20,45].
Overall, enteral nutrition should be initiated after adequate hemodynamic stability has been achieved in critically ill patients. Even in patients receiving vasopressors, cautious initiation of low-dose enteral nutrition may be considered when blood pressure is stable and vasopressor doses are stable or decreasing. However, enteral nutrition should be withheld or discontinued in cases of increasing vasopressor requirements, rising serum lactate levels, or suspected gastrointestinal hypoperfusion or ischemia (Supplement Tables 6, 7).
KQ 5. How should EFI be assessed in critically ill adult patients receiving enteral nutrition?
R10. Assessment of EFI is suggested. EFI should be comprehensively assessed by observing gastrointestinal symptoms, such as vomiting or regurgitation, abdominal distension, diarrhea, abdominal pain, and gastrointestinal bleeding, with GRV measured selectively when clinically indicated. (Expert consensus, strong consensus: 92%)
R11. Routine measurement of GRV is not suggested. (Expert consensus, consensus: 84%)
EFI is a condition in which adequate nutritional delivery cannot be achieved because of impaired gastrointestinal function or gastrointestinal complications, and it may be associated with reduced nutritional intake and worse clinical outcomes [62-64]. Recent guidelines recommend comprehensive assessment of EFI based primarily on clinical symptoms, such as vomiting or regurgitation, abdominal distension, abdominal pain, diarrhea, and gastrointestinal bleeding, rather than relying solely on GRV measurement [1,4,5,65,66].
GRV has traditionally been used in intensive care unit settings to assess aspiration risk and EFI. However, GRV alone does not reliably predict aspiration or clinical outcomes, and omission of routine GRV monitoring has not been associated with increased ventilator-associated pneumonia, mortality, or intensive care unit length of stay [65,66]. Nevertheless, some studies reported increased vomiting events with nonmonitoring strategies, suggesting that symptom-based monitoring remains important [66,67].
Selective GRV measurement may be considered in patients with recurrent vomiting or regurgitation, abdominal distension, abdominal pain, suspected aspiration, or gastrointestinal complications associated with hemodynamic deterioration. Observational studies and meta-analyses have suggested that enteral nutrition may be continued safely in the absence of symptoms even when GRV is within the range of 300–500 mL, and recent international guidelines generally consider GRV ≥500 mL over 4–6 hours to be clinically significant [1,4,5,68,69].
Overall, monitoring of enteral nutrition in critically ill adults should focus primarily on clinical symptoms related to EFI, and routine GRV measurement is not recommended. GRV may be used selectively as an adjunctive assessment tool in patients with suspected EFI or aspiration risk, and decisions regarding interruption of enteral nutrition should be based on comprehensive clinical assessment rather than GRV alone (Supplement Table 8).
KQ 6. In critically ill adult patients receiving enteral nutrition, does continuous feeding, compared with intermittent feeding, affect clinical outcomes?
R12. Continuous feeding may be considered the preferred approach. Intermittent feeding may also be considered in clinically stable patients or when continuous feeding is not feasible. (Low evidence, conditional for, strong consensus: 95%)
Enteral feeding methods are generally classified as continuous feeding and intermittent or bolus feeding. Continuous feeding provides nutrition at a constant rate over time and is commonly used in critically ill patients. A meta-analysis of seven RCTs demonstrated significantly lower intensive care unit mortality in the continuous feeding group than in the intermittent feeding group (relative risk [RR], 0.69; 95% confidence interval [CI], 0.48–0.99) (Fig. 2) [70-76]. Constipation tended to occur more frequently with continuous feeding, although the difference was not statistically significant, whereas other gastrointestinal complications, including vomiting and diarrhea, tended to occur less frequently in the continuous feeding group. In addition, several studies reported that continuous feeding was associated with improved achievement of target calorie and protein delivery, reduced glycemic variability, lower GRV, and improved gastrointestinal tolerance [74,76].
Results regarding aspiration and aspiration pneumonia have been inconsistent across studies. Some studies and meta-analyses reported no significant difference between feeding methods [77,78], whereas others suggested a potential increase in aspiration risk with intermittent or bolus feeding [79,80]. Recent ESPEN practice guidelines and SCCM-ASPEN guidelines recommend preferential consideration of continuous feeding in critically ill patients, particularly in those at high risk of aspiration or with poor tolerance of bolus feeding [1,5,20].
Overall, continuous feeding may provide advantages in feeding stability and gastrointestinal tolerance in critically ill adults and may be preferentially considered in patients at high risk of aspiration or EFI. However, the feeding strategy should be individualized according to the patient’s clinical condition, institutional resources, and intensive care unit practice environment (Supplement Tables 9-11 and Supplement Figs. 1-4).
KQ 7. Does trophic feeding, compared with full feeding, improve clinical outcomes in adult critically ill patients?
R13. Trophic feeding may be considered during the early phase of intensive care unit admission when gastrointestinal function is uncertain or when advancement of enteral nutrition is challenging. (Low evidence, conditional for, strong consensus: 97%)
Trophic feeding is a strategy that provides a limited amount of nutrition to maintain intestinal mucosal integrity and prevent gastrointestinal atrophy; it is generally administered at approximately 10–20 kcal/hr or less than 500 kcal/day [1,20]. Recent international guidelines increasingly describe trophic feeding as an extreme form of hypocaloric feeding during the acute phase of critical illness [4,5,81].
A meta-analysis of three RCTs comparing trophic feeding and full feeding demonstrated no significant differences in mortality (RR, 1.03; 95% CI, 0.85–1.26), pneumonia (RR, 0.98; 95% CI, 0.68–1.43), or overall infection rates (RR, 1.10; 95% CI, 0.89–1.36) (Fig. 3) [82-84]. However, gastrointestinal intolerance, including vomiting, increased GRV, and constipation, tended to occur less frequently in the trophic feeding group.
ESPEN, SCCM-ASPEN, and Korean clinical practice guidelines recommend hypocaloric feeding strategies during the early acute phase of critical illness [4,5,18], and trophic feeding may be considered one form of this restricted-calorie approach. In particular, trophic feeding may serve as an initial strategy to maintain gastrointestinal function and improve feeding tolerance when advancement to full nutritional targets is difficult.
Although trophic feeding did not demonstrate clear benefits in mortality or infectious complications compared with full feeding, it showed potential advantages in reducing gastrointestinal intolerance. Therefore, trophic feeding may be selectively considered during the early acute phase in critically ill patients with uncertain gastrointestinal tolerance or difficulty achieving full nutritional targets, although the current level of evidence remains limited (Supplement Table 12-14 and Supplement Figs. 5-7).
KQ 8. How should aspiration risk be assessed and managed in critically ill adult patients receiving enteral nutrition?
R14. Assessment of aspiration risk should be considered in patients receiving enteral nutrition. (Low evidence, conditional for, strong consensus: 95%)
R15. Post-pyloric feeding should be considered rather than gastric feeding in patients at high risk of aspiration or with gastric feeding intolerance. (Moderate evidence, conditional for, strong consensus: 97%)
R16. The use of prokinetics is suggested in patients at high risk of aspiration or with EFI. (Expert consensus, strong consensus: 95%)
R17. Head-of-bed elevation at 30˚–45˚ and regular oral hygiene are suggested during enteral nutrition in mechanically ventilated patients. (Expert consensus, strong consensus: 100%)
Enteral nutrition in critically ill adults is commonly delivered through gastric or post-pyloric routes. Gastric feeding is the standard approach, but delayed gastric emptying and feeding intolerance may increase the risk of aspiration and pneumonia in high-risk patients [1,5]. SCCM-ASPEN guidelines emphasize the importance of aspiration risk assessment during enteral nutrition [1].
GRV monitoring has traditionally been used to assess aspiration risk [1,66,67]. Three RCTs were identified regarding GRV monitoring; however, one study was excluded from the pooled analysis because it enrolled patients with stroke and evaluated aspiration/vomiting rather than ventilator-associated pneumonia. Therefore, the meta-analysis included two RCTs and showed that routine GRV monitoring did not significantly reduce the incidence of ventilator-associated pneumonia (RR, 1.07; 95% CI, 0.72–1.59) (Fig. 4) [65,85,86]. Recent guidelines also suggest that GRV alone has limited value for aspiration risk assessment, and no standardized aspiration risk assessment tool has yet been established [87,88].
Post-pyloric feeding may be considered in patients at high risk of aspiration or with gastric feeding intolerance [1,5]. A meta-analysis of eight studies comparing gastric and post-pyloric enteral nutrition demonstrated that post-pyloric feeding significantly reduced ventilator-associated pneumonia (RR, 0.63; 95% CI, 0.45–0.86; P=0.004, I²=0%) and duration of mechanical ventilation (mean difference [MD], –1.92 days; 95% CI, –3.33 to –0.51; P=0.008, I²=74%) (Fig. 5) [89-96]. Post-pyloric feeding was also associated with reduced abdominal distension and EFI, although no significant differences were observed in overall pneumonia, mortality, or hospital length of stay. However, technical difficulty and patient characteristics should be considered when selecting the feeding route.
Prokinetics are recommended in patients with EFI [1,20]. Metoclopramide and erythromycin are the most commonly used agents and may improve delayed gastric emptying and feeding tolerance, although their effects on pneumonia prevention remain uncertain [1,5,20,97-99]. In Korea, metoclopramide is commonly available, whereas erythromycin is currently not available for clinical use. Itopride and DA-9701 may also be used as alternative agents, despite limited evidence in critically ill patients [100,101].
Head-of-bed elevation and oral hygiene are the most established nonpharmacologic interventions for aspiration prevention. Previous meta-analyses demonstrated that head-of-bed elevation at 30˚–45˚ reduced ventilator-associated pneumonia [102,103], and oral care using chlorhexidine was also associated with reduced pneumonia risk [104].
Overall, aspiration risk assessment is important in critically ill adults receiving enteral nutrition, although no single parameter reliably predicts aspiration risk. Routine GRV monitoring has limited clinical value, and post-pyloric feeding may be considered in high-risk patients. A multimodal strategy including prokinetics, head-of-bed elevation, and oral hygiene is recommended to reduce aspiration-related complications (Supplement Tables 15-20 and Supplement Figs. 8-12).
KQ 9. What is the optimal method to determine energy requirements in critically ill adult patients?
R18. Indirect calorimetry (IC) is considered for determining energy requirements. (Low evidence, conditional for, strong consensus: 100%)
R19. When IC is unavailable, the use of weight-based formulas (25 kcal/kg/day), predictive equations, and carbon dioxide production (VCO₂)-based estimation methods (in mechanically ventilated patients) is suggested. (Expert consensus, strong consensus: 97%)
Energy requirements in critically ill patients change continuously according to disease severity, inflammatory response, and organ dysfunction; therefore, accurate assessment of energy expenditure is important. Common methods for estimating energy requirements include IC, predictive equations, weight-based formulas, and VCO₂-based estimation methods. ESPEN and SCCM-ASPEN guidelines recommend IC as the reference standard for determining energy requirements in critically ill patients [1,5,20].
A meta-analysis of RCTs comparing IC-guided energy provision with predictive equation- or weight-based approaches demonstrated no significant difference in estimated energy requirements (MD, 25.62 kcal/day; 95% CI, –156.47 to 207.71; P=0.78) or major clinical outcomes, including intensive care unit mortality, hospital mortality, infectious complications, and length of stay (Fig. 6) [24,105-113]. However, actual delivered energy and energy balance tended to be more appropriate in the IC-guided group. Overall heterogeneity among studies was substantial, and the certainty of evidence was low.
Observational studies have reported that predictive equations and weight-based formulas may either underestimate or overestimate energy expenditure depending on the patient population and disease phase [114-125]. In particular, greater inaccuracy has been reported in patients with sepsis, burns, trauma, and liver transplantation because of marked metabolic variability [116-121]. VCO₂-based estimation methods showed relatively small differences compared with IC and may be considered an alternative approach, although they cannot fully replace IC [126]. Weight-based formulas are easy to apply in routine practice, but their accuracy may be limited in patients with edema or obesity. In addition, recent studies suggested that individualized energy delivery strategies increased nutritional delivery without consistently improving major clinical outcomes [127].
IC remains the preferred method for determining energy requirements in critically ill adults because it provides the most accurate assessment of energy expenditure, although its impact on clinical outcomes remains uncertain. Repeated measurements may be helpful when feasible. When IC is unavailable, weight-based formulas, predictive equations, or VCO₂-based estimation methods may be selectively applied according to the patient’s clinical condition (Supplement Tables 21-24 and Supplement Figs. 13-15).
KQ 10. Does enteral fish oil supplementation improve clinical outcomes in critically ill adults?
R20. Routine enteral fish oil supplementation is not recommended. (Low evidence, conditional against, strong consensus: 100%)
R21. Enteral fish oil supplementation may be considered in perioperative patients or those at high risk for infection (e.g., patients undergoing cardiac surgery or those with abdominal sepsis). (Low evidence, conditional for, strong consensus: 91%)
Enteral fish oil supplementation containing eicosapentaenoic acid and docosahexaenoic acid may modulate inflammatory responses and promote resolution of inflammation and has been suggested to reduce infectious complications and shorten hospital stay [128-131]. However, whether these physiological effects consistently translate into improved clinical outcomes remains uncertain [131,132]. ESPEN and SCCM-ASPEN guidelines do not recommend routine enteral fish oil supplementation in critically ill adults [1,5].
A meta-analysis of seven RCTs demonstrated that enteral fish oil supplementation did not significantly reduce intensive care unit mortality (RR, 0.90; 95% CI, 0.59–1.40) or hospital mortality (RR, 0.95; 95% CI, 0.71–1.28) (Fig. 7) [133-139]. Intensive care unit length of stay was significantly shorter in the fish oil group; however, substantial heterogeneity among studies limits interpretation of this finding. Some studies also reported trends toward improvement in hospital length of stay, Sequential Organ Failure Assessment (SOFA) score, and incidence of septic shock, although statistical significance was not consistently demonstrated. Overall, the certainty of evidence was low to moderate because of heterogeneity in study populations, dosing regimens, and duration of supplementation.
Enteral fish oil supplementation has not demonstrated clear mortality benefits in critically ill adults, and current evidence does not support its routine use in the general intensive care unit population. However, selective use may be considered in specific patient populations, including perioperative patients and those at high risk of infectious complications, although further studies are needed (Supplement Tables 25-27, and Supplement Figs. 16-19).
KQ 11. Does additional immune-modulating enteral nutrition with arginine and glutamine affect clinical outcomes in critically ill adults?
R22. Routine enteral arginine supplementation is not recommended. Enteral arginine supplementation may be considered in patients with severe trauma or in postoperative critically ill patients. (Expert consensus, strong consensus: 97%)
R23. Routine enteral glutamine supplementation is not recommended. (Expert consensus, strong consensus: 95%)
Immune-modulating enteral nutrition containing specific nutrients, such as arginine, glutamine, and nucleotides, has been used to modulate immune function, regulate inflammatory responses, and maintain intestinal mucosal integrity [140,141]. However, whether these physiological effects consistently translate into improved clinical outcomes remains uncertain. ESPEN guidelines do not recommend routine use of arginine-containing immune-modulating formulas in critically ill adults, and SCCM-ASPEN guidelines also suggest limiting their use to selected populations, such as patients with severe trauma or surgical critical illness [1,5].
Systematic reviews of arginine-containing enteral immunonutrition have reported improvements in immunological parameters and reductions in postoperative infectious complications and pneumonia [142]. However, most studies involved selected surgical populations, including patients undergoing gastric cancer surgery, and the independent effect of arginine alone remains difficult to determine. Therefore, current evidence supports only selective use in patients with severe trauma or postoperative critical illness rather than routine supplementation in the general intensive care unit population.
Meta-analyses of enteral glutamine supplementation demonstrated possible reductions in hospital length of stay, but no significant improvements in mortality or infectious complications were observed [143]. In addition, interpretation of the results is limited by substantial heterogeneity in study populations, dosing regimens, and duration of supplementation. Other studies suggested potential benefits in intestinal permeability and oxidative stress in selected patient groups, but consistent mortality benefits have not been demonstrated [143-147].
Nucleotides have mainly been studied as components of combined immune-modulating formulas, making their independent clinical effects difficult to evaluate. Clinical evidence regarding nucleotide supplementation in critically ill adults remains very limited [141,148-150].
Current evidence does not support routine supplementation with enteral arginine or glutamine in critically ill adults because clear benefits in mortality and infectious complications have not been demonstrated. Arginine supplementation may be selectively considered in specific surgical conditions, such as severe trauma or postoperative critical illness, whereas routine use in the general intensive care unit population is not recommended. Likewise, routine enteral glutamine supplementation is not recommended because clinically meaningful benefits remain uncertain beyond possible reductions in hospital length of stay (Supplement Tables 28, 29).
KQ 12. In which situations can fiber-containing enteral formulas be used in critically ill adult patients?
R24. Routine use of fiber-containing enteral formulas is not suggested. (Expert consensus, strong consensus: 97%)
R25. In hemodynamically stable patients with preserved gastrointestinal function and persistent diarrhea, the use of fiber-containing enteral formulas is suggested. (Expert consensus, strong consensus: 100%)
Dietary fiber in enteral formulas may help maintain intestinal mucosal integrity and reduce EFI by modulating the gut microbiota and producing short-chain fatty acids [151-154]. Several clinical studies and meta-analyses have suggested that fiber supplementation may reduce the frequency and severity of diarrhea and improve feeding tolerance [154-157]. Soluble fiber has also been associated with potential benefits in glucose and lipid metabolism [152]. However, recommendations from international guidelines remain inconsistent. ESPEN and the Canadian Clinical Practice Guidelines concluded that current evidence is insufficient to support routine use of fiber-containing enteral formulas in critically ill patients [5,20,158]. In contrast, SCCM-ASPEN guidelines suggest the use of soluble fiber in hemodynamically stable patients with diarrhea during enteral nutrition [1]. Systematic reviews have also reported that soluble fiber appears safe and may reduce diarrhea in hemodynamically stable critically ill adults [159].
Insoluble fiber, however, may delay intestinal transit and increase intraluminal pressure, raising concerns about complications such as nonocclusive bowel ischemia in patients with hemodynamic instability or severe gastrointestinal dysmotility [160,161]. Most fiber-containing enteral formulas currently used in Korea contain a mixture of soluble and insoluble fiber, although direct comparative evidence by fiber type remains limited.
Current evidence does not support routine use of fiber-containing enteral formulas in all critically ill adults. However, in hemodynamically stable patients with preserved gastrointestinal function and persistent diarrhea after exclusion of non-nutritional causes, enteral formulas containing soluble fiber may be selectively considered (Supplement Tables 30, 31).
KQ 13. Does probiotic supplementation affect clinical outcomes in critically ill adults?
R26. Routine use of probiotics is not recommended. (Low evidence, conditional against, strong consensus: 100%)
Probiotics have been investigated as a strategy to modulate the gut microbiota, maintain intestinal barrier function, and reduce infectious complications in critically ill patients. A meta-analysis of 18 RCTs demonstrated that probiotic supplementation did not significantly reduce intensive care unit mortality, 28-/30-day mortality, or overall infection rates compared with control groups (Fig. 8) [162-179]. However, probiotic supplementation showed trends toward reductions in pneumonia, ventilator-associated pneumonia, and intensive care unit length of stay, although substantial heterogeneity was observed among studies. Constipation tended to decrease in the probiotic group, whereas no significant difference was observed in diarrhea incidence.
The included studies showed marked variability in probiotic strains, dosing regimens, administration routes, and treatment duration. In addition, study quality and design standardization were limited, resulting in overall low certainty of evidence. Accordingly, SCCM-ASPEN and Canadian Critical Care guidelines do not recommend routine use of probiotics in critically ill adults [1,180].
Probiotic supplementation may provide potential benefits in some infection-related outcomes; however, clear improvements in mortality or major clinical outcomes have not been consistently demonstrated. Given the substantial heterogeneity and potential risk of bias among studies, current evidence does not support routine use of probiotics in critically ill adults (Supplement Tables 32-34 and Supplement Figs. 20-23).
KQ 14. When should PN be initiated in critically ill adults when oral intake and enteral nutrition are not feasible?
R27. In patients unable to receive oral intake or enteral nutrition, initiation of PN within 3–7 days of intensive care unit admission should be considered. (Moderate evidence, conditional for, strong consensus: 92%)
R28. In patients with severe malnutrition, early initiation of PN is suggested. (Expert consensus, strong consensus: 97%)
PN is an alternative nutritional strategy for critically ill adults when oral intake and enteral nutrition are not feasible [5]. However, early PN during the acute phase of critical illness may be associated with overfeeding, hyperglycemia, and infectious complications; therefore, the timing of initiation requires careful consideration [1,3,181-183].
SCCM-ASPEN guidelines recommend considering early PN in patients with malnutrition or high nutritional risk when oral intake or enteral nutrition is not possible, whereas withholding PN during the first 7 days may be acceptable in well-nourished patients [4,5]. Subsequently, the CALORIES and NUTRIREA-2 trials demonstrated no significant differences in mortality or infectious complications between early enteral nutrition and PN strategies [184,185].
A meta-analysis of two RCTs comparing early and delayed PN, the EPaNIC trial and early PN trial, demonstrated no significant differences in intensive care unit mortality, hospital mortality, or long-term mortality between groups (Fig. 9) [50,186]. Early PN was associated with reduced hypoglycemia but increased infectious complications and longer duration of mechanical ventilation. These findings should be interpreted cautiously because calorie delivery and patient characteristics differed across studies.
In critically ill adults who cannot receive oral intake or enteral nutrition, initiation of PN within 3–7 days after intensive care unit admission may be considered in patients with adequate baseline nutritional status. In contrast, early PN may be selectively considered in patients with severe malnutrition or high nutritional risk to prevent further nutritional deterioration. PN should preferably be initiated at a low dose with careful monitoring of blood glucose and electrolytes, followed by gradual advancement according to clinical tolerance (Supplement Tables 35-37 and Supplement Figs. 24-26).
KQ 15. In candidates for early PN, what is the appropriate target caloric intake?
R29. Hypocaloric PN (≤70% of estimated energy requirements or ≤20 kcal/kg/day) is suggested during the early phase of intensive care unit stay (within the first week), with subsequent gradual advancement according to the clinical course. (Expert consensus, strong consensus: 100%)
During the early phase of critical illness, acute stress responses and increased endogenous energy production may increase the risk of metabolic complications, such as hyperglycemia, hepatic steatosis, and infectious complications, when excessive caloric intake is provided [187]. Accordingly, hypocaloric feeding strategies have been proposed during the initial phase of PN to avoid overfeeding.
A meta-analysis involving critically ill patients, including surgical and trauma populations, demonstrated that hypocaloric PN strategies (15–20 kcal/kg/day) were associated with fewer infectious complications and shorter hospital stays [188]. In addition, several RCTs reviewed in the SCCM-ASPEN guidelines reported no significant difference in mortality between hypocaloric and normocaloric feeding strategies, although hypocaloric feeding was associated with reduced hyperglycemia [189-192].
ESPEN guidelines recommend hypocaloric nutrition during the first week of intensive care unit stay in patients unable to receive oral intake or enteral nutrition, generally targeting less than 70% of estimated energy requirements [5,20]. Similarly, SCCM-ASPEN guidelines recommend hypocaloric PN during the first week of intensive care unit stay, defined as ≤20 kcal/kg/day or less than 80% of estimated energy requirements [1].
In critically ill adults requiring early PN, initiation with hypocaloric feeding during the first 7 days of intensive care unit stay appears reasonable. Energy delivery may subsequently be advanced gradually toward target requirements according to the patient’s clinical condition and metabolic stability. Careful monitoring for hyperglycemia, electrolyte imbalance, and refeeding syndrome is required during this period (Supplement Table 38).
KQ 16. Does supplementation with micronutrients and antioxidants affect clinical outcomes in critically ill adult patients?
R30. Micronutrients and vitamins should be routinely provided to meet daily requirements; when PN is used, they should be included at the recommended daily intake level. (Expert consensus, strong consensus: 100%)
R31. Additional supplementation with micronutrients and antioxidants above the recommended intake is not recommended. (Moderate evidence, conditional against, strong consensus: 92%)
R32. Routine high-dose vitamin C supplementation is not recommended. (Moderate evidence, conditional against, consensus: 78%)
R33. High-dose selenium supplementation is not recommended. (Low evidence, conditional against, strong consensus: 95%)
R34. Routine high-dose antioxidant supplementation, including vitamin D, thiamine, and N-acetylcysteine (NAC), is not recommended. (Low evidence, conditional against, strong consensus: 90%)
Micronutrients and vitamins play essential roles in metabolic regulation, antioxidant defense, and immune function, and deficiencies may contribute to organ dysfunction and increased complications in critically ill patients [193,194]. ESPEN guidelines and ASPEN expert consensus statements recommend routine provision of micronutrients and vitamins at the recommended daily intake level during PN in critically ill adults [5,20,194,195]. In contrast, routine supplementation above recommended daily requirements is not supported because evidence of clinical benefit is insufficient [1,5,20].
A meta-analysis including 64 RCTs demonstrated that micronutrient and antioxidant supplementation was associated with reduced 28-/30-day mortality, lower pneumonia incidence, and improved SOFA scores; however, no significant differences were observed in intensive care unit mortality or hospital mortality (Fig. 10) [196-259]. Considerable heterogeneity was present across most outcomes because of differences in patient populations, dosing regimens, duration of supplementation, and combination strategies.
Among individual micronutrients, high-dose vitamin C showed potential benefits in pneumonia reduction and shorter duration of mechanical ventilation in some studies, particularly in patients undergoing cardiovascular surgery, in whom possible reductions in 28-/30-day mortality were observed [196-220]. However, substantial heterogeneity and concerns about an increased need for renal replacement therapy have been reported, and current evidence remains insufficient to support routine use in the general intensive care unit population.
High-dose selenium, vitamin D, thiamine, NAC, and other antioxidant combinations demonstrated possible improvements in selected physiological or laboratory parameters, but consistent benefits in mortality or major clinical outcomes have not been demonstrated [221-259].
Adequate provision of micronutrients and vitamins at recommended daily intake levels remains important in critically ill adults. However, routine high-dose supplementation above recommended requirements is not supported because clinically meaningful benefits remain inconsistent and substantial heterogeneity exists among studies. Subgroup findings suggesting potential benefits of high-dose vitamin C in specific populations, particularly patients undergoing cardiovascular surgery, should be interpreted cautiously and require further validation (Supplement Tables 39-42 and Supplement Figs. 27-29).
KQ 17. Which laboratory parameters should be monitored in critically ill adult patients receiving nutrition therapy?
R35. Blood glucose should be measured immediately after admission or initiation of nutritional therapy and at least every 4 hours during the first 48 hours. The suggested target blood glucose range is 140–180 mg/dL, and insulin therapy is suggested if blood glucose persistently exceeds 180 mg/dL, with institutional discretion for initiation up to 200 mg/dL. (Expert consensus, strong consensus: 97%)
R36. Blood electrolytes (phosphate, potassium, magnesium, sodium, chloride) should be measured at least once daily during the first week of nutritional therapy, with early phosphate measurement suggested within 6–12 hours of admission. (Expert consensus, strong consensus: 95%)
R37. Liver function tests should be measured twice weekly during the initial phase of nutritional therapy and at least once weekly during the stable phase thereafter. (Expert consensus, strong consensus: 100%)
R38. Serum triglyceride levels should be measured once or twice weekly during nutritional therapy. In particular, close monitoring is suggested in patients receiving lipid-containing PN or lipid-based medications. (Expert consensus, strong consensus: 95%)
R39. Prealbumin is suggested as a supplementary marker for assessing response to nutritional therapy, and weekly measurement together with C-reactive protein (CRP) is suggested. (Expert consensus, consensus: 87%)
R40. In patients at high risk of vitamin and trace element deficiencies, clinicians should assess whether thiamine, vitamin C, copper, selenium, zinc, and other essential micronutrients are being supplied adequately and monitor levels when necessary (e.g., prolonged continuous renal replacement therapy [CRRT] for >2 weeks, severe burns, malabsorption, malnutrition, chronic alcoholism, or significant fluid drainage). (Expert consensus, strong consensus: 95%)
R41. Measurement of nitrogen balance is suggested to assess protein adequacy, although its use is limited in dialysis patients. (Expert consensus, strong consensus: 91%)
Appropriate laboratory monitoring is important in critically ill adults receiving nutritional therapy because metabolic alterations and nutrition-related complications commonly occur during intensive care unit care [20,260]. Although direct comparative studies are limited, abnormal laboratory findings are closely associated with clinical course and prognosis, supporting the need for systematic monitoring of key laboratory parameters.
ESPEN guidelines recommend measuring blood glucose immediately after intensive care unit admission or initiation of nutritional therapy and at least every 4 hours during the first 48 hours [20,260]. The recommended target glucose range is 140–180 mg/dL, and persistent hyperglycemia (>180 mg/dL) has been associated with poor clinical outcomes and requires insulin therapy [20,260-262]. Conversely, hypoglycemia (<70 mg/dL) is also associated with increased mortality [20]. In Korean intensive care units, insulin initiation thresholds of approximately 200 mg/dL are also commonly used in practice. Therefore, this guideline recommends maintaining blood glucose within the target range of 140–180 mg/dL while considering insulin therapy when blood glucose persistently exceeds 180 mg/dL, with institutional discretion for initiation up to 200 mg/dL depending on local protocols and clinical judgment.
Electrolyte monitoring is particularly important for prevention and early detection of refeeding syndrome. Hypophosphatemia is a hallmark feature of refeeding syndrome and may contribute to cardiac failure, respiratory failure, and neurological complications. Accordingly, early phosphate measurement within 6–12 hours after intensive care unit admission or initiation of nutritional therapy is recommended, followed by at least daily monitoring during the first week [20,260,263]. Hypokalemia and hypomagnesemia may also occur during refeeding and often require frequent monitoring and replacement, particularly during the early phase of nutritional therapy. Measurement every 6 hours during the first 24 hours may be considered in high-risk patients, followed by at least daily monitoring during the first week [20,260,263]. Sodium and chloride should also be monitored because of their relationship with fluid balance and acid-base status [260].
Liver dysfunction during nutritional therapy may be associated with overfeeding, sepsis, shock, hypoxia, and medication use. Excessive energy delivery has been associated with cholestasis and elevated liver enzyme levels, particularly when energy intake exceeds approximately 26–28 kcal/kg/day [260,264]. Therefore, liver function tests, including aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and bilirubin, are suggested twice weekly during the early phase of nutritional therapy and at least weekly thereafter during the stable phase [260,263,265].
Hypertriglyceridemia may develop in association with lipid-containing PN, prolonged propofol infusion, excessive carbohydrate administration, or sepsis. Serum triglyceride levels are therefore suggested to be monitored once or twice weekly, especially in patients receiving intravenous lipid emulsions or lipid-based medications [260,265]. Reduction or discontinuation of lipid administration may be considered when triglyceride levels exceed 400–500 mg/dL [266].
Prealbumin has a relatively short half-life and may reflect short-term changes in nutritional status; however, it is strongly influenced by acute inflammation and should therefore be interpreted together with CRP [260]. Several studies have demonstrated associations between low or decreasing prealbumin levels and increased disease severity, shock, and poor prognosis [267-271]. Recent studies also suggest that dynamic changes in prealbumin may serve as a useful supplementary marker for assessing response to nutritional therapy [272]. Nevertheless, routine use may be limited by cost and practical considerations.
Patients receiving prolonged CRRT (>2 weeks) are at increased risk of water-soluble vitamin and trace element losses. Reduced levels of vitamin C, selenium, zinc, and copper have been reported in these patients [273,274]. Similarly, patients with severe burns may experience substantial trace element losses through wound exudates, potentially impairing wound healing and immune function [275]. Therefore, patients with prolonged CRRT, severe burns, malabsorption, malnutrition, chronic alcoholism, or significant fluid losses should be assessed for adequate supply and potential deficiencies of thiamine, vitamin C, selenium, copper, and zinc when clinically indicated.
Nitrogen balance remains one representative method for assessing the adequacy of protein delivery. Negative nitrogen balance has been associated with muscle wasting and poor clinical outcomes, and improvement in nitrogen balance has been associated with improved survival in some studies [276-279]. However, interpretation of nitrogen balance is limited because accurate measurement requires 24-hour urinary urea nitrogen collection and may be influenced by renal function, dialysis, urine output, and inflammatory status. In particular, interpretation is limited in patients undergoing dialysis or CRRT because actual nitrogen losses may not be fully reflected [265].
Laboratory monitoring during nutritional therapy is essential for early detection of nutrition-related complications, such as refeeding syndrome, overfeeding, hyperglycemia, and micronutrient deficiencies. Repeated assessment of blood glucose, electrolytes, liver function, triglycerides, prealbumin, and micronutrient status according to the patient’s clinical condition and phase of nutritional therapy is therefore important (Supplement Table 43).
KQ 18. What are strategies for assessing and preventing refeeding syndrome in critically ill adults?
R42. Structured screening for high risk of refeeding syndrome is suggested after intensive care unit admission. (Expert consensus, strong consensus: 97%)
R43. In patients at risk of refeeding syndrome, measurement of serum phosphate, potassium, and magnesium before and during the early phase of nutritional therapy, with supplementation when deficient and frequent reassessment, is suggested. (Expert consensus, strong consensus: 97%)
R44. In patients at risk of refeeding syndrome, initiation of nutrition with caloric restriction (100–150 g of glucose or 10–20 kcal/kg during the first 24 hours), followed by gradual advancement every 1–2 days, is suggested. (Expert consensus, strong consensus: 97%)
R45. In patients at risk of refeeding syndrome, administration of thiamine before initiation of nutritional therapy is suggested. (Expert consensus, strong consensus: 100%)
Refeeding syndrome is a metabolic complication that occurs when nutritional support is restarted after prolonged malnutrition or starvation. It is characterized by hypophosphatemia, hypokalemia, hypomagnesemia, thiamine deficiency, and fluid shifts [1,5,280-285]. These abnormalities usually develop within 72 hours after initiation of nutritional therapy and may result in severe complications, including arrhythmia, heart failure, respiratory failure, neurological dysfunction, and death. Refeeding syndrome may occur during both enteral nutrition and PN, and refeeding hypophosphatemia has been reported in 7%–62% of critically ill patients [284-287].
Patients with prolonged inadequate nutritional intake, significant recent weight loss, low body weight, baseline electrolyte abnormalities, severe illness, or major surgery are considered at high risk for refeeding syndrome [282,284,285]. ASPEN consensus recommendations provide structured criteria for patients at moderate and high risk and recommend systematic screening (Supplement Table 44) [280]. ESPEN and SCCM-ASPEN guidelines also emphasize early risk assessment and gradual nutritional advancement strategies [1,5,281-283,288].
During prolonged starvation, body stores of phosphate, potassium, magnesium, and thiamine become depleted while insulin secretion remains suppressed. After initiation of nutritional therapy, increased insulin secretion promotes rapid intracellular shifts of glucose and electrolytes, resulting in decreased serum concentrations [280,285,289-291]. Simultaneously, sodium and water retention may increase the risk of fluid overload and cardiovascular complications. Hypophosphatemia may impair myocardial and respiratory muscle function, whereas hypokalemia and hypomagnesemia are associated with life-threatening arrhythmias [280,285,289-291]. Thiamine deficiency may lead to lactic acidosis, heart failure (wet beriberi), and Wernicke–Korsakoff syndrome.
In high-risk patients, excessive caloric delivery during the initial phase of nutritional therapy may accelerate insulin-mediated electrolyte shifts and increase the risk of refeeding syndrome. Several studies have reported increased incidence of refeeding syndrome when initial caloric intake exceeded 20 kcal/kg/day, with higher mortality observed in patients with greater refeeding risk [284,291-294]. Therefore, ESPEN and SCCM-ASPEN guidelines recommend initiation of nutritional therapy with hypocaloric feeding (10–20 kcal/kg/day or 100–150 g/day of glucose), followed by gradual advancement according to clinical tolerance [1,5,280-283,292,293].
Electrolyte monitoring is a key component of prevention strategies. In high-risk patients, serum phosphate, potassium, and magnesium should be measured before initiation of nutritional therapy and monitored every 6–12 hours during at least the first 72 hours, followed by at least daily monitoring during the first week [1,260,280,288]. Aggressive supplementation and reassessment are required when deficiencies or rapid declines are detected.
Thiamine is an essential cofactor in glucose metabolism, and deficiency may result in lactic acidosis, heart failure, and Wernicke encephalopathy. Because thiamine requirements increase after initiation of nutritional therapy, international guidelines recommend administration of 100–300 mg/day beginning at least 30 minutes before nutritional support in high-risk patients and continuing for several days [1,5,280-282,285,289,295]. Although RCTs have not consistently demonstrated improved major clinical outcomes with thiamine supplementation [296,297], prophylactic administration is generally recommended because of its favorable safety profile, low cost, and potential to prevent severe thiamine deficiency-related complications. Refeeding syndrome is a potentially fatal complication in critically ill adults, and early risk identification and preventive strategies are essential. Structured screening, close electrolyte monitoring and replacement, gradual advancement of nutritional therapy starting with hypocaloric feeding, and prophylactic thiamine administration are recommended in patients at risk of refeeding syndrome (Supplement Tables 44, 45).
KQ 19. In patients with acute respiratory failure, including ARDS or acute lung injury (ALI), does enteral nutrition enriched with anti-inflammatory lipids affect clinical outcomes?
R46. Routine use of enteral formulas enriched with anti-inflammatory lipids, including omega-3 fatty acids and borage oil, is not recommended. (Moderate evidence, conditional against, strong consensus: 92%)
Enteral formulas enriched with anti-inflammatory lipids were developed to modulate inflammatory responses and attenuate lung injury through supplementation with eicosapentaenoic acid, docosahexaenoic acid, γ-linolenic acid (borage oil), and antioxidants. These formulations have been suggested to improve oxygenation and reduce organ dysfunction by decreasing inflammatory eicosanoid production, modulating neutrophil activation, and reducing alveolar-capillary membrane injury [129,298-300].
A meta-analysis of six RCTs evaluating anti-inflammatory lipid-enriched enteral nutrition in patients with ARDS or ALI showed no significant differences in 28-/60-day mortality (pooled RR, 1.23; 95% CI, 0.89–1.69; P=0.21), intensive care unit length of stay (MD, –0.90 days; 95% CI, –4.37 to 2.57; P=0.64), or ventilator-free days (MD, –0.70 days; 95% CI, –3.37 to 1.97; P=0.61) (Fig. 11) [135,139,301-304]. Some small studies reported improvements in SOFA score or Multiple Organ Dysfunction Score and reductions in new organ failure [303,304]. However, larger studies failed to demonstrate improvements in major clinical outcomes, and some even suggested potentially unfavorable effects [301]. Interpretation of the results is limited by heterogeneity in feeding protocols, formula composition, and patient populations.
Recent systematic reviews and meta-analyses have also shown that immune-modulating enteral formulas enriched with anti-inflammatory lipids do not significantly reduce mortality, and their effects on intensive care unit length of stay and duration of mechanical ventilation remain inconsistent [129,298-300]. Accordingly, both SCCM-ASPEN and ESPEN guidelines do not recommend routine use of these formulations in patients with ARDS or ALI [1,20,301,302,305,306].
Current evidence does not consistently support beneficial effects of anti-inflammatory lipid-enriched enteral formulas on major clinical outcomes in patients with ARDS or ALI, and some studies have reported potentially harmful outcomes. Therefore, routine replacement of standard enteral nutrition with these formulations is not recommended (Supplement Tables 46-49 and Supplement Figs. 30-32).
KQ 20. What is the optimal protein provision in critically ill adults with AKI?
R47. In patients with AKI (stage 1–3) who are not receiving renal replacement therapy, initial protein provision of 0.8–1.0 g/kg/day is suggested, with gradual advancement up to 1.2–1.3 g/kg/day according to the patient’s catabolic state and nutritional status. (Expert consensus, strong consensus: 95%)
R48. In patients receiving CRRT, protein provision of 1.5–1.7 g/kg/day is suggested. (Expert consensus, strong consensus: 95%)
AKI occurs in approximately 40%–60% of critically ill patients and is associated with prolonged intensive care unit stay and increased mortality [307]. Critical illness induces systemic inflammation and hypercatabolism, leading to accelerated protein breakdown and negative nitrogen balance, which are often more pronounced in patients with AKI [1,20]. Therefore, preservation of lean body mass and minimization of nitrogen loss are considered important goals of nutritional therapy in critically ill patients with AKI.
However, recent evidence suggests that routine high-protein feeding during the acute phase may not provide clear clinical benefits in patients with AKI who are not receiving renal replacement therapy [308,309]. Post hoc analyses of the EFFORT Protein trial reported that higher protein delivery (≥1.5–2.2 g/kg/day) in patients with nondialysis AKI was associated with increased 60-day mortality compared with standard protein provision (≤1.2 g/kg/day) [310-312]. Recent meta-analyses also demonstrated that high protein intake did not improve mortality, intensive care unit length of stay, or duration of mechanical ventilation and was associated with increased blood urea nitrogen levels [313,314]. In contrast, some studies suggested potential benefits in selected patients with stage III AKI or individualized protein strategies guided by nitrogen balance [106,315,316].
Current evidence suggests that routine high-protein feeding should not be universally applied during the acute phase of AKI in patients who are not receiving renal replacement therapy. An initial protein provision of approximately 0.8–1.0 g/kg/day, followed by gradual advancement up to 1.2–1.3 g/kg/day according to catabolic status, nutritional condition, and clinical course, appears to be a reasonable approach.
In contrast, patients receiving CRRT experience substantial amino acid and protein losses through the dialysis membrane, together with ongoing systemic catabolism, which increases the risk of negative nitrogen balance and muscle wasting [317-319]. Observational studies have suggested that higher protein intake may be associated with improved survival in patients receiving CRRT [320]. ESPEN guidelines recommend protein provision of at least 1.5 g/kg/day in patients receiving CRRT, with possible advancement up to 1.7 g/kg/day when clinically appropriate [20,307,310,311,313,314,321]. Individualization of protein delivery according to the patient’s metabolic and clinical condition is also considered important [307,317-319,321].
Protein provision in critically ill adults with AKI should be individualized according to renal replacement status, catabolic burden, nutritional status, and clinical course. Moderate protein provision appears appropriate in patients with non-CRRT AKI during the acute phase, whereas higher protein delivery is generally required in patients receiving CRRT because of increased protein losses and catabolism (Supplement Tables 50, 51).
KQ 21. Does high protein provision affect clinical outcomes in critically ill adults with liver failure?
R49. High protein provision (1.2–1.5 g/kg/day) is suggested in patients with liver failure. (Expert consensus, strong consensus: 91%)
R50. In hyperacute liver failure, protein provision may be delayed for 24–48 hours, with gradual initiation suggested thereafter. (Expert consensus, strong consensus: 95%)
R51. Routine use of branched-chain amino acid (BCAA)-enriched protein supplementation is not recommended in patients with liver failure and hepatic encephalopathy. However, oral or enteral BCAA-enriched protein supplementation may be considered in those with suspected protein intolerance or recurrent hepatic encephalopathy. (Expert consensus, strong consensus: 93%)
Patients with liver failure commonly develop protein depletion and sarcopenia because of increased protein catabolism and reduced protein synthesis, both of which are associated with poor clinical outcomes [5,322-324]. In particular, patients with cirrhosis and chronic liver failure frequently experience negative nitrogen balance and progressive muscle loss, whereas unnecessary protein restriction may further aggravate catabolism and malnutrition [325-328]. Current international guidelines do not recommend routine protein restriction in patients with liver failure. ESPEN guidelines recommend protein provision of approximately 1.2–1.5 g/kg/day in patients with liver failure and cirrhosis [5,322-324].
Some studies have suggested that higher protein intake or BCAA supplementation may improve nutritional parameters, such as muscle mass, handgrip strength, and serum albumin levels [329-332]. However, consistent improvements in mortality or long-term clinical outcomes have not been demonstrated. In addition, regular meal patterns and late-evening snacks may reduce overnight protein catabolism and nitrogen loss, whereas increased protein intake combined with exercise may help preserve muscle mass in patients with sarcopenia or sarcopenic obesity [322,333].
In hyperacute liver failure, elevated serum ammonia levels (>150 μmol/L) are associated with cerebral edema and increased intracranial pressure. Because patients are often metabolically unstable during the early phase, a stepwise nutritional approach may be required [334-339]. Accordingly, temporary delay or restriction of protein provision during the initial 24–48 hours, followed by gradual reintroduction, has been proposed. After protein reintroduction, close monitoring of ammonia levels and neurological status is necessary.
Routine protein restriction is also not recommended in patients with hepatic encephalopathy. RCTs have shown that normal-protein diets do not worsen hepatic encephalopathy [328], whereas protein restriction may aggravate catabolism and malnutrition. However, some patients may demonstrate protein intolerance, and in such cases, plant-based protein or BCAA-enriched protein supplementation at approximately 0.25 g/kg/day may be considered [322,338,340]. Systematic reviews and meta-analyses have shown that BCAA supplementation may improve symptoms of hepatic encephalopathy, although consistent benefits in mortality or long-term outcomes have not been demonstrated [341-344].
Long-term oral BCAA supplementation has been associated with improved event-free survival and quality of life in patients with advanced cirrhosis [345,346]. However, clear clinical benefits of intravenous BCAA administration in acute hepatic encephalopathy have not been established [339,343,344]. Therefore, BCAA supplementation may be selectively considered in patients with suspected protein intolerance or recurrent hepatic encephalopathy. In patients with obesity-associated nonalcoholic fatty liver disease or nonalcoholic steatohepatitis, protein provision of approximately 1.0–1.2 g/kg/day based on adjusted body weight may be considered, whereas higher protein intake may be required in those with malnutrition or sarcopenia [5,338].
Sufficient protein provision (1.2–1.5 g/kg/day) is generally preferred over routine protein restriction in critically ill adults with liver failure. However, temporary restriction followed by gradual advancement may be appropriate during the early unstable phase of hyperacute liver failure. Routine protein restriction is also not recommended in patients with hepatic encephalopathy, although selective use of BCAA-enriched protein supplementation may be considered in patients with suspected protein intolerance or recurrent hepatic encephalopathy (Supplement Table 52).
KQ 22. Does early enteral nutrition, compared with delayed enteral nutrition, improve clinical outcomes in adult trauma patients?
R52. Early enteral nutrition is suggested in patients with acute traumatic brain injury and acute spinal cord injury once hemodynamic stability has been achieved and gastrointestinal function is adequate. (Very low evidence, conditional for, strong consensus: 100%)
R53. Early enteral nutrition is suggested in patients with acute spinal cord injury once hemodynamic stability has been achieved and gastrointestinal function is adequate. (Expert consensus, strong consensus: 100%)
R54. Early enteral nutrition is suggested in patients with abdominal trauma who are hemodynamically stable and have confirmed or restored gastrointestinal continuity. (Expert consensus, strong consensus: 97%)
Trauma patients develop a marked catabolic response and increased metabolic demands immediately after injury, leading to rapid protein breakdown and negative nitrogen balance. These metabolic alterations are associated with muscle wasting, impaired immune function, and increased infectious complications, and delayed nutritional support may contribute to worse clinical outcomes. Therefore, initiation of enteral nutrition after hemodynamic stabilization has been advocated. In patients with traumatic brain injury, energy and protein requirements increase early after injury, and persistent nutritional deficits may be associated with infection, organ dysfunction, and delayed neurological recovery [347]. International guidelines, including the American College of Surgeons Trauma Quality Programs (ACS TQP) 2023 guidelines, ESPEN 2019/2023 guidelines, SCCM-ASPEN 2016 guidelines, and ESICM 2017 guidelines, recommend initiation of early enteral nutrition within 24–72 hours after hemodynamic stabilization [1,5,20,45,347,348]. A meta-analysis of two RCTs demonstrated that early enteral nutrition did not significantly reduce mortality, pneumonia, or hospital length of stay compared with delayed feeding (Fig. 12) [349,350]. However, early enteral nutrition was shown to be feasible and potentially beneficial without significant safety concerns. Because the number of studies and sample sizes were limited, the certainty of evidence was considered very low.
In patients with acute spinal cord injury, increased nitrogen loss and rapid muscle wasting occur early after injury, resulting in prolonged negative nitrogen balance [351-353]. Historically, nutritional support was often delayed because of concerns about ileus and EFI. However, recent studies and international guidelines recommend initiation of enteral nutrition as early as feasible, generally within 48 hours after hemodynamic stabilization [1,5,20,45,351,352]. Although direct randomized evidence remains limited, early enteral nutrition is considered clinically reasonable for maintaining gastrointestinal integrity and preventing nutritional deterioration.
In patients with abdominal trauma, disruption of gut barrier integrity and bacterial translocation may occur after injury or surgery, while profound catabolism develops simultaneously [5,354]. Therefore, early enteral nutrition has been advocated when gastrointestinal continuity is preserved or surgically restored and when contraindications, such as bowel ischemia, uncontrolled bleeding, or mechanical obstruction, are absent [5,45,355,356]. ESICM, ESPEN, SCCM-ASPEN, and recent trauma nutrition guidelines recommend initiation of enteral nutrition within 24–48 hours, and up to 72 hours, after hemodynamic stabilization [1,5,20,45,355,356]. Some studies have suggested potential benefits in reducing infections and preserving gastrointestinal function. The European Society for Trauma and Emergency Surgery Recommendations on Acute Care Surgery and Trauma Intensive Care guideline additionally suggested initiation of low-volume trickle feeding as early as feasible once gastrointestinal continuity has been surgically restored [355].
Although direct evidence demonstrating a survival benefit of early enteral nutrition in trauma patients remains limited, international guidelines consistently recommend initiation of enteral nutrition as early as possible after hemodynamic stabilization. In particular, in patients with traumatic brain injury, acute spinal cord injury, and abdominal trauma, early enteral nutrition may help reduce cumulative energy and protein deficits and preserve gastrointestinal function. Therefore, its application should be individualized according to the patient’s hemodynamic status and gastrointestinal function (Supplement Tables 53-55, and Supplement Figs. 33-35).
KQ 23. In critically ill adults with sepsis, does early enteral nutrition, compared with delayed enteral nutrition, improve clinical outcomes?
R55. Early enteral nutrition is suggested in patients with sepsis once hemodynamic stability has been achieved, with gradual advancement according to clinical status. (Expert consensus, strong consensus: 100%)
In patients with sepsis, systemic inflammation and tissue hypoperfusion may lead to intestinal mucosal injury, gut microbiota dysbiosis, and bacterial translocation, all of which may contribute to multiple organ dysfunction and poor clinical outcomes [1,45,357]. Enteral nutrition may help attenuate these pathophysiological processes by preserving intestinal mucosal integrity, maintaining gut-associated immune function, and preventing mucosal atrophy [1]. Accordingly, international guidelines recommend initiation of enteral nutrition as early as possible after hemodynamic stabilization.
Several studies have suggested that early enteral nutrition initiated within 24–48 hours after intensive care unit admission or sepsis diagnosis may be associated with shorter duration of mechanical ventilation, reduced intensive care unit length of stay, and shorter hospital stay compared with delayed enteral nutrition [358-361]. In addition, studies in patients with surgical sepsis have reported improvements in immunological parameters associated with early enteral nutrition [362]. However, the effect on mortality has been inconsistent across studies, and interpretation is limited by heterogeneity in patient populations and feeding strategies.
In patients with septic shock or hemodynamic instability, concerns remain about the risk of bowel ischemia due to impaired splanchnic perfusion [363-365]. In particular, aggressive early feeding may increase the risk of gastrointestinal complications [57,364]. Nevertheless, recent studies have demonstrated that trophic enteral nutrition initiated after stabilization of blood pressure and tissue perfusion, even in patients receiving vasopressors, was not associated with increased rates of severe bowel ischemia or intestinal necrosis and may be associated with shorter duration of mechanical ventilation and intensive care unit stay [57,366].
Although the current evidence remains limited and heterogeneous, early enteral nutrition appears feasible and relatively safe in patients with sepsis and may provide potential benefits, including reduced intensive care unit stay and shorter duration of mechanical ventilation. Therefore, initiation of enteral nutrition as early as possible after hemodynamic stabilization, generally within 24–48 hours, with low-dose initiation and gradual advancement according to gastrointestinal tolerance and clinical condition, is considered a reasonable strategy (Supplement Tables 56, 57).
KQ 24. What is the optimal nutritional therapy for critically ill adults with obesity?
R56. Early initiation of enteral nutrition is suggested once hemodynamic stability has been achieved. (Expert consensus, strong consensus: 100%)
R57. IC is suggested as the preferred method for measuring energy requirements. (Expert consensus, strong consensus: 95%)
R58. When IC is unavailable, hypocaloric nutrition of 20–25 kcal/kg/day based on adjusted body weight is suggested during the acute phase, with gradual advancement toward measured energy expenditure during the recovery phase. (Expert consensus, strong consensus: 95%)
R59. Protein provision of ≥1.3 g/kg/day based on adjusted body weight is suggested. (Expert consensus, strong consensus: 95%)
Nutritional therapy in critically ill adults with obesity should aim to minimize loss of lean body mass while avoiding overfeeding. In critically ill patients with obesity, energy calculation based on actual body weight may lead to overfeeding, whereas protein provision is often insufficient. Therefore, a hypocaloric, high-protein strategy has been proposed as the preferred nutritional approach [5,367-378].
There is no evidence supporting delayed enteral nutrition solely because of obesity. Early enteral nutrition after hemodynamic stabilization is considered appropriate. Observational studies have suggested that initiation of enteral nutrition within 24–48 hours after intensive care unit admission may be associated with shorter duration of mechanical ventilation and reduced intensive care unit length of stay, although mortality benefits have not been consistently demonstrated [369,371,375,376]. International guidelines also recommend early enteral nutrition after hemodynamic stabilization [1,5].
IC is considered the most accurate method for determining energy requirements in critically ill patients with obesity. Predictive equations may substantially overestimate or underestimate actual energy expenditure in this population [379,380]. When IC is unavailable, initiation of hypocaloric feeding using 20–25 kcal/kg/day based on adjusted body weight (= ideal body weight + 0.25 × [actual body weight – ideal body weight]) has been proposed to avoid overfeeding during the acute phase [1,5,380-383]. Gradual advancement according to the clinical course, recovery phase, and changes in energy expenditure is considered reasonable.
Adequate protein provision is a key component of nutritional therapy to reduce muscle wasting and intensive care unit-acquired weakness. ESPEN guidelines recommend protein provision of approximately 1.3 g/kg/day based on adjusted body weight [5,367,368,372-374,377,378,384]. Several studies have suggested that high-protein feeding based on ideal or adjusted body weight may improve nitrogen balance and help preserve lean body mass [1,377,378]. However, very high protein provision has not consistently demonstrated improvements in major clinical outcomes and may be associated with potential harm in some patient populations, indicating the need for individualized approaches [372,373].
In critically ill adults with obesity, early enteral nutrition after hemodynamic stabilization and assessment of energy requirements using IC are recommended whenever feasible. When IC is unavailable, initiation of hypocaloric feeding based on adjusted body weight together with a high-protein strategy targeting ≥1.3 g/kg/day is considered a reasonable approach (Supplement Tables 58, 59).
Discussion
Nutritional therapy is an essential component of critical care management. Accordingly, several international societies and research groups, including the ESPEN, ESICM, SCCM-ASPEN, ASPEN, and the Canadian Critical Care Nutrition group, have published evidence-based clinical practice guidelines and systematic reviews on nutritional therapy in critically ill patients [1,4,5,20,45,385]. However, these guidelines differ in the timing and route of nutritional therapy, energy and protein targets, and disease-specific nutritional strategies. In addition, some recommendations are difficult to apply directly in Korean intensive care units because of differences in medical resources, nutritional support systems, medication availability, and clinical practice patterns. Accordingly, KSPEN developed evidence-based clinical practice guidelines for nutritional therapy in critically ill adults that reflect Korean clinical practice. In 2024, KSPEN published a preliminary Part I guideline addressing seven key clinical questions [18]. The current guideline expands on the previous version and provides a comprehensive guideline covering broader aspects of nutritional therapy in critically ill adults.
One strength of the present guideline is that it incorporated relatively recent evidence by primarily including studies published after 2010. Whenever possible, recommendations were based on RCTs, systematic reviews, and meta-analyses. For clinical topics with insufficient RCT evidence or substantial heterogeneity among studies, recommendations were developed using narrative evidence synthesis and expert consensus. This approach allowed broad clinical coverage while maintaining evidence-based recommendation development. The present guideline also sought to reflect Korean intensive care unit practice patterns and domestic clinical environments. Although efforts were made to include Korean studies and domestic clinical data whenever available, high-quality Korean evidence remains limited. Most available domestic studies were observational or retrospective, and large-scale, well-controlled RCTs involving Korean critically ill patients were scarce. Therefore, many recommendations were still based largely on international evidence and did not substantially differ from existing ESPEN or ASPEN guidelines.
Nevertheless, several recommendations were adapted to address practical issues specific to Korea. For example, although IC is recommended as the preferred method for energy assessment, its routine use remains limited because of restricted equipment availability and operational barriers in many Korean intensive care units [5,105]. In addition, because intravenous erythromycin is currently unavailable in Korea, recommendations regarding prokinetic agents were adapted to reflect domestically available medications, such as metoclopramide, itopride, and DA-9701. Differences in intensive care unit staffing, nutrition support team availability, enteral formula accessibility, and institutional resources were also considered during recommendation development. Therefore, some recommendations differ from international guidelines in practical implementation and clinical applicability. Another important strength of the present guideline is its emphasis on individualized nutritional therapy according to hemodynamic status, metabolic phase, nutritional risk, organ dysfunction, and disease-specific conditions rather than uniform application of aggressive nutritional strategies. This approach is consistent with emerging evidence suggesting that excessive early caloric delivery may not improve clinical outcomes and may potentially increase metabolic complications during the acute phase of critical illness [185,186].
Limitations
Several limitations should be acknowledged. First, because the guideline addressed a broad range of clinical questions, the certainty of evidence varied considerably across recommendations. In several areas, including immune-modulating nutrition, micronutrient supplementation, probiotics, and disease-specific nutritional therapy, evidence heterogeneity and limited high-quality studies resulted in low or very low certainty of evidence. Consequently, many recommendations were presented as conditional recommendations or expert consensus statements rather than strong evidence-based recommendations. Second, because of the relative lack of Korean-specific evidence on nutritional therapy in critically ill adults, adaptation of international evidence was unavoidable in several sections. Differences in healthcare systems, intensive care unit resources, patient characteristics, and nutritional practices may influence the direct applicability of international evidence to Korean clinical practice. Additional multicenter studies involving Korean critically ill patients are needed to establish higher-quality domestic evidence. Third, because these guidelines addressed a broad range of nutritional issues in critically ill adults, different methodological approaches were used according to evidence availability and quality. Some key clinical questions were supported by formal systematic reviews and meta-analyses, whereas others relied primarily on narrative evidence synthesis and expert consensus. Nevertheless, efforts were made to ensure transparency and methodological rigor through structured literature review, multidisciplinary participation, application of GRADE methodology, and independent external review.
Despite these limitations, the present guideline has several strengths. First, it represents a multidisciplinary effort involving physicians, pharmacists, nurses, dietitians, and methodology experts. Second, the guideline incorporates both evidence synthesis and practical applicability in Korean intensive care units. Third, detailed supplementary materials, including search strategies, evidence summaries, risk of bias assessments, and meta-analyses, were provided to enhance transparency and reproducibility. Fourth, the recommendations cover a wide spectrum of nutritional issues encountered in daily intensive care unit practice and may facilitate standardized nutritional management in critically ill adults. Implementation of some recommendations, including IC-guided nutritional assessment and post-pyloric feeding, may be limited by institutional resources, staffing, and equipment availability. Therefore, flexibility and adaptation according to local intensive care unit resources may be necessary. Because evidence regarding critical care nutrition continues to evolve, periodic revision and updating of these guidelines will be necessary. Additional Korean multicenter clinical studies and implementation research are also needed to improve the quality of evidence and evaluate the clinical impact of guideline adherence in Korean intensive care units.
Conclusion
These guidelines provide practical, evidence-based recommendations for nutritional therapy in critically ill adults while reflecting current international evidence and Korean clinical practice. The guideline may contribute to improved standardization, consistency, and quality of nutritional support in critically ill patients in Korea and may serve as a foundation for future research and implementation of evidence-based critical care nutrition practices.
Authors’ contribution
Conceptualization: JGL, YMS, SHL. Data curation: JGL, YMS, SHL, YTJ, HJL, JYP, NJC, JMS, JYL, JYK, JYJ, YWS, EJP, HJK, JYC, BK, YO, ICL, JYL, ARK, JYL, SEK, TSH, KMK. Formal analysis: all authors. Investigation: all authors. Methodology: all authors. Project administration: JGL, YMS, SHL. Resources: all authors. Supervision: JGL, SHL. Validation: all authors. Visualization: all authors. Writing–original draft: JGL. Writing–review & editing: all authors. All authors read and approved the final manuscript.
Conflict of interest
Yun Tae Jung has served as an Editorial Board Member of the Annals of Clinical Nutrition and Metabolism. However, he was not involved in the peer review process or decision-making regarding publication. Otherwise, no other potential conflict of interest relevant to this article was reported.
Funding
None.
Data availability
No new data were created or analyzed in this study. Data sharing is not applicable to this article.
Acknowledgments
The authors would like to thank the Korean Society for Parenteral and Enteral Nutrition (KSPEN) for supporting the development of these clinical practice guidelines. We also acknowledge the methodological support provided by the National Evidence-based Healthcare Collaborating Agency (NECA). In addition, we sincerely thank the medical librarians at Asan Medical Center for their assistance with the literature search process.
Supplementary materials
Supplementary materials can be found via https://doi.org/10.15747/ACNM.26.0059
Supplement Table 1.
Literature search strategy for KQ1: candidates for nutritional therapy in critically ill adult patients
Supplement Table 2.
Summary of included studies evaluating candidates for nutritional therapy in critically ill adult patients (KQ1)
Supplement Table 3.
Literature search strategy for KQ2: screening and assessment of malnutrition and nutritional risk in critically ill adult patients
Supplement Table 4.
Literature search strategy for KQ3: timing of nutritional therapy initiation in critically ill adult patients
Supplement Table 5.
Summary of included studies comparing the timing of nutritional therapy initiation in critically ill adult patients (KQ3)
Supplement Table 6.
Literature search strategy for KQ4: delayed initiation or discontinuation of enteral nutrition in critically ill adult patients
Supplement Table 7.
Summary of included studies evaluating enteral nutrition in critically ill adult patients receiving vasopressors (KQ4)
Supplement Table 8.
Literature search strategy for KQ5: assessment of enteral feeding intolerance in critically ill adult patients receiving enteral nutrition
Supplement Table 9.
Literature search strategy for KQ6: continuous versus intermittent enteral feeding in critically ill adult patients
Supplement Table 10.
Summary of randomized controlled trials comparing continuous versus intermittent enteral feeding in critically ill adult patients (KQ6)
Supplement Table 11.
Summary of clinical outcomes comparing continuous versus intermittent enteral feeding in critically ill adult patients (KQ6)
Supplement Table 12.
Literature search strategy for KQ7: trophic versus full feeding in critically ill adult patients
Supplement Table 13.
Summary of randomized controlled trials comparing trophic versus full feeding in critically ill adult patients (KQ7)
Supplement Table 14.
Summary of clinical outcomes comparing trophic versus full feeding in critically ill adult patients (KQ7)
Supplement Table 15.
Literature search strategy for KQ8: aspiration risk assessment and management in critically ill adult patients receiving enteral nutrition
Supplement Table 16.
Summary of randomized controlled trials evaluating gastric residual volume-based monitoring in critically ill adult patients receiving enteral nutrition (KQ8)
Supplement Table 17.
Summary of clinical outcomes from randomized controlled trials evaluating gastric residual volume-based monitoring in critically ill adult patients receiving enteral nutrition (KQ8)
Supplement Table 18.
Summary of randomized controlled trials comparing post-pyloric versus gastric enteral nutrition in critically ill adult patients (KQ8)
Supplement Table 19.
Summary of clinical outcomes comparing post-pyloric versus gastric enteral nutrition in critically ill adult patients (KQ8)
Supplement Table 20.
Summary of studies evaluating gastric residual volume-based monitoring, aspiration risk assessment, and non-feeding route-based preventive strategies in critically ill adult patients receiving enteral nutrition (KQ8)
Supplement Table 21.
Literature search strategy for KQ9: assessment of energy requirements in critically ill adult patients
Supplement Table 22.
Characteristics of randomized controlled trials included in the meta-analysis evaluating indirect calorimetry-guided versus predictive equation-guided energy provision in critically ill adult patients (KQ9)
Supplement Table 23.
Summary of clinical outcomes from randomized controlled trials evaluating indirect calorimetry-guided versus predictive equation-guided energy provision in critically ill adult patients (KQ9)
Supplement Table 24.
Summary of observational studies comparing indirect calorimetry with predictive equations in critically ill adult patients (KQ9)
Supplement Table 25.
Literature search strategy for KQ10: enteral fish oil supplementation in critically ill adult patients
Supplement Table 26.
Summary of randomized controlled trials evaluating enteral fish oil supplementation in critically ill adult patients (KQ10)
Supplement Table 27.
Summary of clinical outcomes from randomized controlled trials evaluating enteral fish oil supplementation in critically ill adult patients (KQ10)
Supplement Table 28.
Literature search strategy for KQ11: immune-modulating enteral nutrition in critically ill adults
Supplement Table 29.
Summary of studies evaluating immune-modulating enteral nutrition in critically ill adults (KQ11)
Supplement Table 30.
Literature search strategy for KQ12: fiber-containing enteral formulas in critically ill adult patients
Supplement Table 31.
Summary of studies comparing fiber-containing versus fiber-free enteral formulas in critically ill adult patients (KQ12)
Supplement Table 32.
Literature search strategy for KQ13: probiotics supplementation in critically ill adults
Supplement Table 33.
Characteristics of randomized controlled trials evaluating probiotics supplementation in critically ill adults (KQ13)
Supplement Table 34.
Summary of clinical outcomes from randomized controlled trials evaluating probiotics supplementation in critically ill adults (KQ13)
Supplement Table 35.
Literature search strategy for KQ14: timing of parenteral nutrition initiation in critically ill adult patients
Supplement Table 36.
Summary of randomized controlled trials comparing early versus delayed parenteral nutrition in critically ill adult patients (KQ14)
Supplement Table 37.
Summary of clinical outcomes from randomized controlled trials comparing early versus delayed parenteral nutrition in critically ill adult patients (KQ14)
Supplement Table 38.
Literature search strategy for KQ15: target caloric intake during early parenteral nutrition in critically ill adult patients
Supplement Table 39.
Literature search strategy for KQ16: micronutrient and antioxidant supplementation in critically ill adult patients
Supplement Table 40.
Characteristics of randomized controlled trials evaluating micronutrient and antioxidant supplementation in critically ill adults (KQ16)
Supplement Table 41.
Summary of clinical outcomes from randomized controlled trials evaluating micronutrient and antioxidant supplementation in critically ill adults (KQ16)
Supplement Table 42.
Results of meta-analysis according to micronutrient and antioxidant category in critically ill adults (KQ16)
Supplement Table 43.
Literature search strategy for KQ17: monitoring parameters during nutrition therapy in critically ill adult patients
Supplement Table 44.
ASPEN consensus criteria for identifying adult patients at risk of refeeding syndrome (KQ18)
Supplement Table 45.
Literature search strategy for KQ18: assessment and prevention of refeeding syndrome in critically ill adults
Supplement Table 46.
Literature search strategy for KQ19: anti-inflammatory lipid-containing enteral nutrition formulations in patients with ARDS and ALI
Supplement Table 47.
Characteristics of randomized controlled trials evaluating anti-inflammatory lipid-containing enteral nutrition formulations in patients with ARDS and ALI (KQ19)
Supplement Table 48.
Composition of anti-inflammatory lipid-containing enteral nutrition formulations evaluated in randomized controlled trials (KQ19)
Supplement Table 49.
Organ failure-related outcomes reported in randomized controlled trials evaluating anti-inflammatory lipid-containing enteral nutrition formulations in patients with ARDS and ALI (KQ19)
Supplement Table 50.
Literature search strategy for KQ20: protein provision in critically ill adults with acute kidney injury
Supplement Table 51.
Summary of studies evaluating protein provision in critically ill adults with acute kidney injury (KQ20)
Supplement Table 52.
Literature search strategy for KQ21: protein provision in critically ill adults with liver failure
Supplement Table 53.
Literature search strategy for KQ22: early versus delayed enteral nutrition in adult trauma patients
Supplement Table 54.
Characteristics of randomized controlled trials comparing early versus delayed enteral nutrition in patients with traumatic brain injury (KQ22)
Supplement Table 55.
Summary of clinical outcomes from randomized controlled trials comparing early versus delayed enteral nutrition in patients with traumatic brain injury (KQ22)
Supplement Table 56.
Literature search strategy for KQ23: early versus delayed enteral nutrition in critically ill adult patients with sepsis
Supplement Table 57.
Characteristics of studies evaluating early versus delayed enteral nutrition in critically ill adult patients with sepsis (KQ23)
Supplement Table 58.
Literature search strategy for KQ24: nutritional therapy in critically ill adults with obesity
Supplement Table 59.
Summary of studies evaluating nutritional therapy in critically ill adults with obesity (KQ24)
Supplement Fig. 1.
PRISMA flow diagram of studies evaluating continuous versus intermittent enteral feeding in critically ill adult patients (KQ6)
Supplement Fig. 2.
Risk of bias assessment using the Cochrane Risk of Bias 1.0 tool for randomized controlled trials evaluating continuous versus intermittent enteral feeding in critically ill adult patients (KQ6)
Supplement Fig. 3.
GRADE Summary of Findings generated using GRADEpro GDT for continuous versus intermittent enteral feeding in critically ill adult patients (KQ6)
Supplement Fig. 4.
Forest plots comparing continuous versus intermittent enteral feeding in critically ill adult patients (KQ6)
Supplement Fig. 5.
PRISMA flow diagram of studies included in the meta-analysis for KQ7
Supplement Fig. 6.
Risk of bias assessment using the Cochrane Risk of Bias 1.0 tool for randomized controlled trials comparing trophic versus full feeding in critically ill adult patients (KQ7)
Supplement Fig. 7.
GRADE Summary of Findings generated using GRADEpro GDT for trophic versus full feeding in critically ill adult patients (KQ7)
Supplement Fig. 8.
PRISMA flow diagram of studies included in the meta-analysis evaluating gastric residual volume-based monitoring (KQ8)
Supplement Fig. 9.
PRISMA flow diagram of studies included in the meta-analysis comparing post-pyloric versus gastric enteral nutrition (KQ8)
Supplement Fig. 10.
Risk of bias assessment using the Cochrane Risk of Bias 1.0 tool for randomized controlled trials evaluating gastric residual volume-based monitoring in critically ill adult patients receiving enteral nutrition (KQ8)
Supplement Fig. 11.
Risk of bias assessment using the Cochrane Risk of Bias 1.0 tool for randomized controlled trials comparing post-pyloric versus gastric enteral nutrition in critically ill adult patients (KQ8)
Supplement Fig. 12.
GRADE Summary of Findings generated using GRADEpro GDT for post-pyloric versus gastric enteral nutrition in critically ill adult patients (KQ8)
Supplement Fig. 13.
PRISMA 2020 flow diagram of studies included in the meta-analysis evaluating energy requirement assessment methods in critically ill adult patients (KQ9)
Supplement Fig. 14.
Risk of bias assessment using the Cochrane Risk of Bias 1.0 tool for randomized controlled trials evaluating indirect calorimetry-guided versus predictive equation-guided energy provision in critically ill adult patients (KQ9)
Supplement Fig. 15.
GRADE Summary of Findings generated using GRADEpro GDT for indirect calorimetry-guided versus predictive equation-guided energy provision in critically ill adult patients (KQ9)
Supplement Fig. 16.
PRISMA flow diagram of studies included in the meta-analysis evaluating enteral fish oil supplementation in critically ill adult patients (KQ10)
Supplement Fig. 17.
Risk of bias assessment using the Cochrane Risk of Bias 1.0 tool for randomized controlled trials evaluating enteral fish oil supplementation in critically ill adult patients (KQ10)
Supplement Fig. 18.
Forest plots showing additional clinical outcomes of enteral fish oil supplementation in critically ill adult patients (KQ10)
Supplement Fig. 19.
GRADE Summary of Findings generated using GRADEpro GDT for enteral fish oil supplementation in critically ill adult patients (KQ10)
Supplement Fig. 20.
PRISMA flow diagram of studies included in the meta-analysis evaluating probiotics supplementation in critically ill adults (KQ13)
Supplement Fig. 21.
Risk of bias assessment using the Cochrane Risk of Bias 1.0 tool for randomized controlled trials evaluating probiotics supplementation in critically ill adults (KQ13)
Supplement Fig. 22.
GRADE Summary of Findings generated using GRADEpro GDT for probiotics supplementation in critically ill adults (KQ13)
Supplement Fig. 23.
Forest plots summarizing additional clinical outcomes of probiotics supplementation in critically ill adults (KQ13).
Supplement Fig. 24.
Forest plots summarizing additional clinical outcomes of probiotics supplementation in critically ill adults (KQ13)
Supplement Fig. 25.
Risk of bias assessment using the Cochrane Risk of Bias 1.0 tool for randomized controlled trials comparing early versus delayed parenteral nutrition in critically ill adult patients (KQ14)
Supplement Fig. 26.
GRADE Summary of Findings generated using GRADEpro GDT for early versus delayed parenteral nutrition in critically ill adult patients (KQ14)
Supplement Fig. 27.
PRISMA 2020 flow diagram of studies included in the meta-analysis evaluating micronutrient and antioxidant supplementation in critically ill adults (KQ16)
Supplement Fig. 28.
Risk of bias assessment using the Cochrane Risk of Bias 1.0 tool for randomized controlled trials evaluating micronutrient and antioxidant supplementation in critically ill adults (KQ16)
Supplement Fig. 29.
GRADE Summary of Findings generated using GRADEpro GDT for micronutrient and antioxidant supplementation in critically ill adults (KQ16)
Supplement Fig. 30.
PRISMA 2020 flow diagram of studies included in the meta-analysis evaluating anti-inflammatory lipid-containing enteral nutrition formulations in patients with ARDS and ALI (KQ19)
Supplement Fig. 31.
Risk of bias assessment using the Cochrane Risk of Bias 1.0 tool for randomized controlled trials evaluating anti-inflammatory lipid-containing enteral nutrition formulations in patients with ARDS and ALI (KQ19)
Supplement Fig. 32.
GRADE Summary of Findings generated using GRADEpro GDT for anti-inflammatory lipid-containing enteral nutrition formulations in patients with ARDS and ALI (KQ19)
Supplement Fig. 33.
PRISMA 2020 flow diagram of studies included in the systematic review and meta-analysis evaluating early versus delayed enteral nutrition in patients with traumatic brain injury (KQ22)
Supplement Fig. 34.
Risk of bias assessment using the Cochrane Risk of Bias 1.0 tool for randomized controlled trials comparing early versus delayed enteral nutrition in patients with traumatic brain injury (KQ22)
Supplement Fig. 35.
GRADE Summary of Findings generated using GRADEpro GDT for early versus delayed enteral nutrition in patients with traumatic brain injury (KQ22)
Fig. 1.
GRADE framework for determining certainty of evidence. GRADE, Grading of Recommendations Assessment, Development and Evaluation.
Fig. 2.
Forest plots of mortality outcomes comparing continuous versus intermittent enteral feeding in critically ill adult patients. M-H, Mantel-Haenszel; CI, confidence interval; ICU, intensive care unit.
Fig. 3.
Forest plots of synthesized outcomes comparing trophic versus full feeding in critically ill adult patients: (A) mortality, (B) pneumonia, and (C) any infection. M-H, Mantel-Haenszel; CI, confidence interval.
Fig. 4.
Forest plot comparing the incidence of ventilator-associated pneumonia according to GRV monitoring in critically ill adult patients receiving enteral nutrition. GRV, gastric residual volume; M-H, Mantel-Haenszel; CI, confidence interval.
Fig. 5.
Forest plots comparing post-pyloric versus gastric enteral nutrition in critically ill adult patients: (A) ventilator-associated pneumonia, (B) duration of mechanical ventilation, and (C) feeding intolerance. M-H, Mantel-Haenszel; CI, confidence interval; SD, standard deviation.
Fig. 6.
Forest plots comparing IC-guided versus predictive equation-guided energy provision in critically ill adult patients: (A) daily energy delivery, (B) daily energy balance, and (C) intensive care unit mortality. IC, indirect calorimetry; SD, standard deviation; PE, predictive equation; IV, inverse variance; M-H, Mantel-Haenszel; CI, confidence interval.
Fig. 7.
Forest plots showing the effects of enteral fish oil supplementation in critically ill adult patients: (A) intensive care unit mortality, (B) hospital mortality, (C) intensive care unit length of stay, and (D) hospital length of stay. M-H, Mantel-Haenszel; CI, confidence interval; SD, standard deviation; IV, inverse variance.
Fig. 8.
Forest plots summarizing the effects of probiotic supplementation in critically ill adults: (A) intensive care unit mortality, (B) 28-/30-day mortality, and (C) incidence of infection. M-H, Mantel-Haenszel; CI, confidence interval.
Fig. 9.
Forest plots comparing early versus delayed PN in critically ill adult patients: (A) intensive care unit mortality, (B) intensive care unit length of stay, and (C) infectious complications. PN, parenteral nutrition; M-H, Mantel-Haenszel; CI, confidence interval; SD, standard deviation; IV, inverse variance.
Fig. 10.
Forest plots showing the effects of micronutrient and antioxidant supplementation in critically ill adults: (A) 28-/30-day mortality and (B) pneumonia. M-H, Mantel-Haenszel; CI, confidence interval.
Fig. 11.
Forest plots showing the effects of anti-inflammatory lipid-containing enteral nutrition formulations in patients with acute respiratory distress syndrome and acute lung injury: (A) 28-/60-day mortality, (B) intensive care unit length of stay, and (C) ventilator-free days. M-H, Mantel-Haenszel; CI, confidence interval; SD, standard deviation; IV, inverse variance.
Fig. 12.
Forest plot comparing mortality between EEN and DEN in patients with traumatic brain injury. EEN, early enteral nutrition; DEN, delayed enteral nutrition; M-H, Mantel-Haenszel; CI, confidence interval.
Table 1.
Definitions of certainty of evidence according to the GRADE approach
Table 2.
GRADE recommendation strength and interpretation
Table 3.
Consensus strength and agreement thresholds
| Consensus strength | Agreement (%) | Recommendation status |
|---|---|---|
| Strong consensus | ≥90 | Accepted |
| Consensus | 75–89 | Accepted |
| Majority consensus | 50–74 | Re-discussion and re-voting required |
| No consensus | <50 | Rejected |
Table 4.
Summary of recommendations
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Nutritional support for critically ill patients by the Korean Society for Parenteral and Enteral Nutrition—part II: a clinical practice guideline
Fig. 1. GRADE framework for determining certainty of evidence. GRADE, Grading of Recommendations Assessment, Development and Evaluation.
Fig. 2. Forest plots of mortality outcomes comparing continuous versus intermittent enteral feeding in critically ill adult patients. M-H, Mantel-Haenszel; CI, confidence interval; ICU, intensive care unit.
Fig. 3. Forest plots of synthesized outcomes comparing trophic versus full feeding in critically ill adult patients: (A) mortality, (B) pneumonia, and (C) any infection. M-H, Mantel-Haenszel; CI, confidence interval.
Fig. 4. Forest plot comparing the incidence of ventilator-associated pneumonia according to GRV monitoring in critically ill adult patients receiving enteral nutrition. GRV, gastric residual volume; M-H, Mantel-Haenszel; CI, confidence interval.
Fig. 5. Forest plots comparing post-pyloric versus gastric enteral nutrition in critically ill adult patients: (A) ventilator-associated pneumonia, (B) duration of mechanical ventilation, and (C) feeding intolerance. M-H, Mantel-Haenszel; CI, confidence interval; SD, standard deviation.
Fig. 6. Forest plots comparing IC-guided versus predictive equation-guided energy provision in critically ill adult patients: (A) daily energy delivery, (B) daily energy balance, and (C) intensive care unit mortality. IC, indirect calorimetry; SD, standard deviation; PE, predictive equation; IV, inverse variance; M-H, Mantel-Haenszel; CI, confidence interval.
Fig. 7. Forest plots showing the effects of enteral fish oil supplementation in critically ill adult patients: (A) intensive care unit mortality, (B) hospital mortality, (C) intensive care unit length of stay, and (D) hospital length of stay. M-H, Mantel-Haenszel; CI, confidence interval; SD, standard deviation; IV, inverse variance.
Fig. 8. Forest plots summarizing the effects of probiotic supplementation in critically ill adults: (A) intensive care unit mortality, (B) 28-/30-day mortality, and (C) incidence of infection. M-H, Mantel-Haenszel; CI, confidence interval.
Fig. 9. Forest plots comparing early versus delayed PN in critically ill adult patients: (A) intensive care unit mortality, (B) intensive care unit length of stay, and (C) infectious complications. PN, parenteral nutrition; M-H, Mantel-Haenszel; CI, confidence interval; SD, standard deviation; IV, inverse variance.
Fig. 10. Forest plots showing the effects of micronutrient and antioxidant supplementation in critically ill adults: (A) 28-/30-day mortality and (B) pneumonia. M-H, Mantel-Haenszel; CI, confidence interval.
Fig. 11. Forest plots showing the effects of anti-inflammatory lipid-containing enteral nutrition formulations in patients with acute respiratory distress syndrome and acute lung injury: (A) 28-/60-day mortality, (B) intensive care unit length of stay, and (C) ventilator-free days. M-H, Mantel-Haenszel; CI, confidence interval; SD, standard deviation; IV, inverse variance.
Fig. 12. Forest plot comparing mortality between EEN and DEN in patients with traumatic brain injury. EEN, early enteral nutrition; DEN, delayed enteral nutrition; M-H, Mantel-Haenszel; CI, confidence interval.
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Nutritional support for critically ill patients by the Korean Society for Parenteral and Enteral Nutrition—part II: a clinical practice guideline
| Certainty of evidence | Definition |
|---|---|
| High | We are very confident that the true effect is close to the estimated effect. |
| Moderate | We are moderately confident in the estimated effect. The true effect is likely to be close to the estimate, but it may be substantially different. |
| Low | Confidence in the estimated effect is limited. The true effect may be substantially different from the estimate. |
| Very low | We have very little confidence in the estimated effect. The true effect is likely to be substantially different from the estimate. |
| Recommendation category (recommendation strength) | Definition | Recommended wording | |
|---|---|---|---|
| Evidence-based recommendation (SR & MA for RCT) | Strong for | The intervention is strongly recommended in most clinical situations after considering the balance between benefits and harms, certainty of evidence, patient values and preferences, and resource utilization. | “We recommend …” |
| Conditional for | The use of the intervention may vary depending on clinical circumstances or patient/social values and preferences; selective or conditional use is suggested. | “… is considered” | |
| Conditional against | The potential harms of the intervention may outweigh the benefits in some clinical situations or patient populations; routine use is not recommended. | “… is not recommended” | |
| Strong against | The harms of the intervention outweigh the benefits in most clinical situations after considering certainty of evidence, values and preferences, and resource utilization. | “We recommend against…” | |
| Inconclusive | The certainty of evidence is too low, or the balance between benefits and harms is highly uncertain or variable; therefore, no recommendation can be made. Clinical judgment should guide decision-making. | “…cannot decide” | |
| Expert consensus | Although direct clinical evidence is limited, recommendations are made based on expert opinion, clinical experience, potential benefits and harms, values and preferences, and feasibility. | “… is suggested” or “… is not suggested” | |
| Consensus strength | Agreement (%) | Recommendation status |
|---|---|---|
| Strong consensus | ≥90 | Accepted |
| Consensus | 75–89 | Accepted |
| Majority consensus | 50–74 | Re-discussion and re-voting required |
| No consensus | <50 | Rejected |
| Section | Recommendation | Evidence/Recommendation/Consensus |
|---|---|---|
| Indications and nutritional risk assessment | R1. Critically ill adult patients expected to stay in the intensive care unit for more than 48 hours are considered at risk for malnutrition, and nutrition therapy is suggested. | Expert consensus/strong consensus |
| R2. Screening for malnutrition or nutritional risk using a structured tool is suggested within 24–48 hours after intensive care unit admission. | Expert consensus/strong consensus | |
| R3. Use of validated tools such as the modified Nutrition Risk in the Critically Ill score or Nutritional Risk Screening 2002 is suggested for nutritional risk screening. | Expert consensus/strong consensus | |
| R4. Standardized assessment and diagnosis using tools such as the Global Leadership Initiative on Malnutrition criteria or Subjective Global Assessment are suggested in patients at risk, followed by appropriate nutrition care planning. | Expert consensus/strong consensus | |
| Timing and initiation of nutritional therapy | R5. Early initiation of nutritional therapy as soon as possible after hemodynamic stabilization is suggested. | Expert consensus/strong consensus |
| R6. Enteral nutrition is suggested as the preferred route, and parenteral nutrition may be applied on an individual basis according to the patient’s clinical condition. | Expert consensus/strong consensus | |
| R7. Initiation of enteral nutrition is not suggested in hemodynamically unstable patients until hemodynamic stability has been achieved. | Expert consensus/strong consensus | |
| R8. Initiation of low-dose enteral nutrition (10–20 mL/hr) is suggested in patients receiving vasopressors when adequate hemodynamic stability has been achieved and vasopressor doses are stable or decreasing. | Expert consensus/strong consensus | |
| R9. Withholding or discontinuation of enteral nutrition is suggested in the following situations. | Expert consensus/strong consensus | |
| · Uncontrolled shock and hypoperfusion: lack of hemodynamic stability, increasing vasopressor requirements, elevated serum lactate levels, or suspected tissue hypoperfusion | ||
| · Uncontrolled life-threatening respiratory failure: severe hypoxemia, hypercapnia, or acidosis | ||
| · Active gastrointestinal bleeding | ||
| · Gastrointestinal dysfunction or severe enteral feeding intolerance: severe abdominal distension, GRV >500 mL over 6 hours, uncontrolled vomiting (with aspiration risk), or diarrhea | ||
| · High-output intestinal fistula or stoma: when safe enteral feeding distal to the fistula or stoma is not feasible | ||
| · Structural gastrointestinal injury: unresolved intestinal perforation, mechanical bowel obstruction, or bowel ischemia | ||
| · Abdominal compartment syndrome | ||
| Enteral nutrition delivery and monitoring | R10. Assessment of EFI is suggested. EFI should be comprehensively assessed by observing gastrointestinal symptoms, such as vomiting or regurgitation, abdominal distension, diarrhea, abdominal pain, and gastrointestinal bleeding, with GRV measured selectively when clinically indicated. | Expert consensus/strong consensus |
| R11. Routine measurement of GRV is not suggested. | Expert consensus/strong consensus | |
| R12. Continuous feeding may be considered the preferred approach. Intermittent feeding may also be considered in clinically stable patients or when continuous feeding is not feasible. | Low evidence/conditional for/strong consensus | |
| R13. Trophic feeding may be considered during the early phase of intensive care unit admission when gastrointestinal function is uncertain or when advancement of enteral nutrition is challenging. | Low evidence/conditional for/strong consensus | |
| R14. Assessment of aspiration risk should be considered in patients receiving enteral nutrition. | Low evidence/conditional for/strong consensus | |
| R15. Post-pyloric feeding should be considered rather than gastric feeding in patients at high risk of aspiration or with gastric feeding intolerance. | Moderate evidence/conditional for/strong consensus | |
| R16. The use of prokinetics is suggested in patients at high risk of aspiration or with enteral feeding intolerance. | Expert consensus/strong consensus | |
| R17. Head-of-bed elevation at 30˚–45˚ and regular oral hygiene are suggested during enteral nutrition in mechanically ventilated patients. | Expert consensus/strong consensus | |
| Energy requirements | R18. IC is considered for determining energy requirements. | Low evidence/conditional for/strong consensus |
| R19. When IC is unavailable, the use of weight-based formulas (25 kcal/kg/day), predictive equations, and VCO₂-based estimation methods (in mechanically ventilated patients) is suggested. | Expert consensus/strong consensus | |
| Formulation of enteral nutrition | R20. Routine enteral fish oil supplementation is not recommended. | Low evidence/conditional for/strong consensus |
| R21. Enteral fish oil supplementation may be considered in perioperative patients or those at high risk for infection (e.g., patients undergoing cardiac surgery or those with abdominal sepsis). | Low evidence/conditional for/strong consensus | |
| R22. Routine enteral arginine supplementation is not recommended. Enteral arginine supplementation may be considered in patients with severe trauma or in postoperative critically ill patients. | Expert consensus/strong consensus | |
| R23. Routine enteral glutamine supplementation is not recommended. | Expert consensus/strong consensus | |
| R24. Routine use of fiber-containing enteral formulas is not suggested. | Expert consensus/strong consensus | |
| R25. In hemodynamically stable patients with preserved gastrointestinal function and persistent diarrhea, the use of fiber-containing enteral formulas is suggested. | Expert consensus/strong consensus | |
| R26. Routine use of probiotics is not recommended. | Low evidence/conditional against/strong consensus | |
| Parenteral nutrition | R27. In patients unable to receive oral intake or enteral nutrition, initiation of PN within 3–7 days of intensive care unit admission should be considered. | Moderate evidence/conditional for/strong consensus |
| R28. In patients with severe malnutrition, early initiation of PN is suggested. | Expert consensus/strong consensus | |
| R29. Hypocaloric PN (≤70% of estimated energy requirements or ≤20 kcal/kg/day) is suggested during the early phase of intensive care unit stay (within the first week), with subsequent gradual advancement according to the clinical course. | Expert consensus/strong consensus | |
| Micronutrients | R30. Micronutrients and vitamins should be routinely provided to meet daily requirements; when PN is used, they should be included at the recommended daily intake level. | Expert consensus/strong consensus |
| R31. Additional supplementation with micronutrients and antioxidants above the recommended intake is not recommended. | Moderate evidence/conditional against/strong consensus | |
| R32. Routine high-dose vitamin C supplementation is not recommended. | Moderate evidence/conditional against/consensus | |
| R33. High-dose selenium supplementation is not recommended. | Low evidence/conditional against/strong consensus | |
| R34. Routine high-dose antioxidant supplementation, including vitamin D, thiamine, and N-acetylcysteine (NAC), is not recommended. | Low evidence/conditional against/strong consensus | |
| Monitoring and metabolic complications | R35. Blood glucose should be measured immediately after admission or initiation of nutritional therapy and at least every 4 hours during the first 48 hours. The suggested target blood glucose range is 140–180 mg/dL, and insulin therapy is suggested if blood glucose persistently exceeds 180 mg/dL, with institutional discretion for initiation up to 200 mg/dL. | Expert consensus/strong consensus |
| R36. Blood electrolytes (phosphate, potassium, magnesium, sodium, chloride) should be measured at least once daily during the first week of nutritional therapy, with early phosphate measurement suggested within 6–12 hours of admission. | Expert consensus/strong consensus | |
| R37. Liver function tests should be measured twice weekly during the initial phase of nutritional therapy and at least once weekly during the stable phase thereafter. | Expert consensus/strong consensus | |
| R38. Serum triglyceride levels should be measured once or twice weekly during nutritional therapy. In particular, close monitoring is suggested in patients receiving lipid-containing PN or lipid-based medications. | Expert consensus/strong consensus | |
| R39. Prealbumin is suggested as a supplementary marker for assessing response to nutritional therapy, and weekly measurement together with C-reactive protein is suggested. | Expert consensus/consensus | |
| R40. In patients at high risk of vitamin and trace element deficiencies, clinicians should assess whether thiamine, vitamin C, copper, selenium, zinc, and other essential micronutrients are being supplied adequately and monitor levels when necessary (e.g., prolonged CRRT for >2 weeks, severe burns, malabsorption, malnutrition, chronic alcoholism, or significant fluid drainage). | Expert consensus/strong consensus | |
| R41. Measurement of nitrogen balance is suggested to assess protein adequacy, although its use is limited in dialysis patients. | Expert consensus/strong consensus | |
| R42. Structured screening for high risk of refeeding syndrome is suggested after intensive care unit admission. | Expert consensus/strong consensus | |
| R43. In patients at risk of refeeding syndrome, measurement of serum phosphate, potassium, and magnesium before and during the early phase of nutritional therapy, with supplementation when deficient and frequent reassessment, is suggested. | Expert consensus/strong consensus | |
| R44. In patients at risk of refeeding syndrome, initiation of nutrition with caloric restriction (100–150 g of glucose or 10–20 kcal/kg during the first 24 hours), followed by gradual advancement every 1–2 days, is suggested. | Expert consensus/strong consensus | |
| R45. In patients at risk of refeeding syndrome, administration of thiamine before initiation of nutritional therapy is suggested. | Expert consensus/strong consensus | |
| Acute respiratory failure | R46. Routine use of enteral formulas enriched with anti-inflammatory lipids, including omega-3 fatty acids and borage oil, is not recommended. | Moderate evidence, conditional against, strong consensus |
| Acute kidney injury | R47. In patients with acute kidney injury (stage 1–3) who are not receiving renal replacement therapy, initial protein provision of 0.8–1.0 g/kg/day is suggested, with gradual advancement up to 1.2–1.3 g/kg/day according to the patient’s catabolic state and nutritional status. | Expert consensus/strong consensus |
| R48. In patients receiving CRRT, protein provision of 1.5–1.7 g/kg/day is suggested. | Expert consensus/strong consensus | |
| Liver failure | R49. High protein provision (1.2–1.5 g/kg/day) is suggested in patients with liver failure. | Expert consensus/strong consensus |
| R50. In hyperacute liver failure, protein provision may be delayed for 24–48 hours, with gradual initiation suggested thereafter. | Expert consensus/strong consensus | |
| R51. Routine use of BCAA-enriched protein supplementation is not recommended in patients with liver failure and hepatic encephalopathy. However, oral or enteral BCAA-enriched protein supplementation may be considered in those with suspected protein intolerance or recurrent hepatic encephalopathy. | Expert consensus/strong consensus | |
| Trauma | R52. Early enteral nutrition is suggested in patients with acute traumatic brain injury once hemodynamic stability has been achieved and gastrointestinal function is adequate. | Very low evidence, conditional for, strong consensus |
| R53. Early enteral nutrition is suggested in patients with acute spinal cord injury once hemodynamic stability is ensured and gastrointestinal function is adequate. | Expert consensus/strong consensus | |
| R54. Early enteral nutrition is suggested in patients with abdominal trauma who are hemodynamically stable and have confirmed or restored gastrointestinal continuity. | Expert consensus/strong consensus | |
| Sepsis | R55. Early enteral nutrition is suggested in patients with sepsis once hemodynamic stability has been achieved, with gradual advancement according to clinical status. | Expert consensus/strong consensus |
| Obesity | R56. Early initiation of enteral nutrition is suggested once hemodynamic stability has been achieved. | Expert consensus/strong consensus |
| R57. Indirect calorimetry is suggested as the preferred method for measuring energy requirements. | Expert consensus/strong consensus | |
| R58. When indirect calorimetry is unavailable, hypocaloric nutrition of 20–25 kcal/kg/day based on adjusted body weight is suggested during the acute phase, with gradual advancement toward measured energy expenditure during the recovery phase. | Expert consensus/strong consensus | |
| R59. Protein provision of ≥1.3 g/kg/day based on adjusted body weight is suggested. | Expert consensus/strong consensus |
Table 1. Definitions of certainty of evidence according to the GRADE approach
GRADE, Grading of Recommendations Assessment, Development and Evaluation.
Table 2. GRADE recommendation strength and interpretation
GRADE, Grading of Recommendations Assessment, Development and Evaluation; SR & MA, systematic review and meta-analysis; RCT, randomized controlled trial.
Table 3. Consensus strength and agreement thresholds
Table 4. Summary of recommendations
GRV, gastric residual volume; EFI, enteral feeding intolerance; IC, indirect calorimetry; VCO₂, carbon dioxide production; PN, parenteral nutrition; CRRT, continuous renal replacement therapy; BCAA, branched-chain amino acid.
