Accuracy of Predictive Formulas vs. Indirect Calorimetry in Estimating Energy Needs of Patients in Intensive Care Units
Round 1
Reviewer 1 Report
Comments and Suggestions for Authors
This study addresses an important and clinically relevant topic, namely the discrepancy between calculated energy requirements and actual nutritional intake in ICU patients. The comparison between indirect calorimetry and predictive formulas is meaningful and aligns with current debates in critical care nutrition. However, several methodological and reporting issues should be addressed to improve the scientific robustness and clarity of the manuscript.
Title: The title addresses a relevant topic but is overly long and structured as a double question, which reduces its clarity. Additionally, the term “actual food consumption” does not appear to be the most appropriate scientific terminology; expressions such as “actual energy intake” would be preferable. It is recommended to simplify and rephrase the title to improve clarity and scientific precision.
Highlights: The highlights are clear and relevant; however, the use of acronyms (e.g., ICU, ESPEN) should be avoided or defined at first mention to improve clarity and accessibility for a broader readership. Simplifying terminology would enhance their effectiveness.
Abstract: The abstract is well structured but presents some limitations. Several acronyms (e.g., ICU, IC, HB, ESPEN, BEE) are used without definition, reducing clarity. The concept of “actual consumption” is not adequately specified. In addition, the results are partly unclear (e.g., correlations) and not sufficiently contextualized from a clinical perspective. Finally, the conclusions appear overstated considering the sample size and the lack of clinical outcomes.
Introduction: The introduction is generally clear and well structured but presents some limitations. The research gap appears to be stated rather than critically supported; the claim that no studies exist on this topic is too strong and not adequately justified by references. A more cautious wording is recommended, along with better support from up-to-date literature. Additionally, some references are outdated (e.g., refs. 5 and 6), and more recent studies should be included to strengthen the scientific background. Materials and Methods: This section presents several methodological issues that require clarification. First, the study design is not explicitly stated (e.g., prospective observational study), making it difficult to properly interpret the methodological framework. The sample size calculation is not adequately reported: key parameters are missing (e.g., “effect size of X” and “standard deviation of Y”), and the justification based on time, budget constraints, and the nature of a master’s thesis is not methodologically appropriate. The definition of “actual energy consumption” remains unclear: it is not specified whether this refers to prescribed, delivered, or effectively absorbed energy intake, despite being a central outcome of the study. Furthermore, the data collection process lacks transparency. Data were obtained from patient records, physicians, and relatives, but no information is provided on how consistency and reliability across these sources were ensured. The use of a 34-item questionnaire is reported; however, no details are provided regarding its validation, development, or psychometric properties, raising concerns about measurement validity. In addition, the sampling strategy is not clearly defined. Although the recruitment period (May–June 2023) is mentioned, it is not specified whether a consecutive, convenience, or other sampling approach was used, limiting the assessment of potential selection bias. Finally, the short observation period (three days, including the first 24–48 hours of ICU admission) may significantly affect the accuracy of energy estimations, given the metabolic instability typical of the acute phase. It is recommended to improve methodological clarity and transparency by explicitly stating the study design, completing the reporting of the sample size calculation, clearly defining key variables, and providing more detailed information on data collection procedures and sampling methods. Results: This section is overall rich in information but lacks clear structure and could be improved in terms of clarity of presentation. In particular, the results should be organized into thematic subsections to facilitate readability and interpretation. For example, it would be helpful to begin with a subsection describing participants’ characteristics (demographic and clinical), followed by a section on nutritional parameters, and finally the results of comparative and agreement analyses between methods (IC, HB, ESPEN). Currently, descriptive data, main findings, and advanced statistical analyses are presented sequentially but in a mixed manner, making it difficult to identify the key results of the study.
From a statistical perspective, several issues should be noted. In particular, a “negative correlation” is reported between IC and HB with r=0.35, which actually indicates a positive correlation, suggesting a potential error in the description of the results (lines 266–267). Moreover, the distinction between correlation and agreement is not always clearly addressed. While the use of Pearson correlation, Bland–Altman analysis, and Passing–Bablok regression is appropriate, the interpretation of these analyses appears partly unclear and redundant. Some information (e.g., biochemical parameters) is mentioned but not presented (“not presented”), reducing the transparency and verifiability of the data. Finally, the results are not adequately contextualized from a clinical perspective. For example, the approximately 500 kcal difference between measured and actual energy intake, although potentially relevant, is not discussed in terms of its clinical implications in critically ill patients.
Discussion: The discussion addresses a clinically relevant topic but presents several issues in terms of interpretation and depth of analysis. First, the authors’ interpretations appear somewhat overly emphatic in relation to the available data. In particular, the emphasis on the use of indirect calorimetry as the preferred method is not fully supported, considering the small sample size, short observation period, and lack of relevant clinical outcomes. Moreover, the claim regarding the uniqueness of the study appears too strong and is not adequately supported by the existing literature, which already includes several studies comparing indirect calorimetry and predictive formulas. The discussion does not consistently maintain a clear distinction between the concepts of correlation and agreement, despite the use of appropriate statistical methods. This may lead to ambiguity in the interpretation of the results. In addition, the discrepancy between estimated energy requirements and actual intake, as highlighted in the results, is only partially discussed and not sufficiently explored in terms of its clinical and organizational implications, for example considering potential barriers to nutrition delivery in ICU settings. Finally, some parts are repetitive and redundant, reducing the overall clarity of the message.
Conclusion: The concluding section presents some issues in terms of both structure and content. First, it would be preferable to present the limitations section before the conclusions, in order to provide a more balanced and contextualized interpretation of the findings. Although some limitations are acknowledged (small sample size, measurements performed within the first 24–48 hours, and population heterogeneity), they are not comprehensively discussed. In particular, important aspects such as the lack of clinical outcomes, potential bias related to the measurement of actual intake, and the single-center nature of the study are not adequately addressed. Furthermore, the conclusions appear somewhat overstated in relation to the available data. The emphasis on the use of indirect calorimetry and the related clinical recommendations are not fully supported, given the study design and its limitations. Overall, it is recommended to reorganize this section by presenting the limitations first and revising the conclusions in a more cautious manner, in line with the study findings.
Tables: The tables and figures present several issues that affect clarity and interpretability. First, the tables are not self-contained: several acronyms (e.g., APACHE II, SOFA, mNUTRIC, PNI, IC, HB) are not defined within the table footnotes but only in the final abbreviations section. This limits readability and does not align with standard reporting practices. Additionally, some tables lack structural clarity. Table 2 mixes different data presentation formats (mean ± standard deviation and median with interquartile ranges) without a clear distinction. Table 3 has a complex and difficult-to-interpret layout, while Table 4 includes an incomplete title and a non-intuitive structure. There are also inconsistencies in numerical formatting (use of commas vs decimal points) and non-uniform reporting of measurement units.
Figures: Figure 1 appears visually dense and combines multiple analyses within a single panel without sufficiently clear labeling. Figure 2 (flow diagram) is overly simplified and could be improved to better align with reporting standards (e.g., STROBE).
Author Response
Dear Reviewer,
In line with your valuable suggestions and the revised flow of the manuscript, the necessary revisions have been made and the overall structure has been improved. All modifications and additions have been clearly highlighted in red throughout the manuscript. The revisions are presented in detail below, point by point.
Response to Reviewer #1:
Comments 1: This study addresses an important and clinically relevant topic, namely the discrepancy between calculated energy requirements and actual nutritional intake in ICU patients. The comparison between indirect calorimetry and predictive formulas is meaningful and aligns with current debates in critical care nutrition. However, several methodological and reporting issues should be addressed to improve the scientific robustness and clarity of the manuscript.
Response 1:
We sincerely thank the reviewer for the valuable comments and for highlighting the clinical relevance of our study. In line with these constructive suggestions, substantial revisions have been made to improve the methodological rigor, clarity, and overall quality of the manuscript.
The Methods section has been significantly expanded, with clearer and more detailed descriptions of the study design, patient selection, and implementation procedures to enhance transparency and reproducibility. In addition, the power analysis has been presented in detail, and it is now clearly stated that the sample size was determined accordingly. Although an adequate sample size was achieved based on this analysis, we explicitly emphasized that larger-scale studies with longer follow-up periods are needed to obtain more robust and generalizable findings. In this context, overly assertive statements have been revised or removed, and a more cautious and scientifically balanced tone has been adopted throughout the manuscript.
In response to the reviewer’s suggestions, the limitations of the study have been thoroughly addressed in both the Discussion and a dedicated Limitations section, ensuring a transparent presentation of methodological constraints and issues related to generalizability. Furthermore, the term “actual nutritional intake” has been clarified and revised as “actual energy intake,” explicitly defined as the energy delivered to patients through clinical nutrition practices (enteral and/or parenteral), rather than estimated or prescribed values.
Additionally, methodological details regarding indirect calorimetry (IC) and predictive equations have been further elaborated, and patient characteristics along with the clinical context have been described more comprehensively. The manuscript has also been carefully revised to reduce redundancy and improve overall readability and flow.
The literature review has been restructured and strengthened, clearly identifying the existing gap in the field, while presenting how our study contributes to this gap and acknowledging its limitations in a balanced manner.
Moreover, the design and resolution quality of tables and figures have been improved, and all visual elements have been revised in accordance with journal standards using MDPI editing services.
Overall, thanks to the reviewer’s valuable feedback, the manuscript has been substantially improved and is now presented in a more transparent, coherent, and methodologically robust manner, with a stronger integration into the current literature.
Comments 2: Title: The title addresses a relevant topic but is overly long and structured as a double question, which reduces its clarity. Additionally, the term “actual food consumption” does not appear to be the most appropriate scientific terminology; expressions such as “actual energy intake” would be preferable. It is recommended to simplify and rephrase the title to improve clarity and scientific precision.
Response 2: In line with the reviewer’s suggestion and the consensus of the other reviewers, the manuscript title has been revised accordingly. The revised title is as follows:“Accuracy of Predictive Formulas vs. Indirect Calorimetry in Estimating Energy Needs of Intensive Care Unit Patients.”In addition, the terminology used throughout the manuscript has been reviewed, and the expression “actual food consumption” has been replaced with “actual energy intake.” To clearly define this term, the following sentence has been added to the Methods section:
“In this study, ‘energy intake’ refers to the energy actually delivered to patients in clinical practice, rather than prescribed or theoretically calculated values.” (Lines 204–205)
Comments 3: Highlights: The highlights are clear and relevant; however, the use of acronyms (e.g., ICU, ESPEN) should be avoided or defined at first mention to improve clarity and accessibility for a broader readership. Simplifying terminology would enhance their effectiveness.
Response 3:
We have revised the highlights to define all acronyms at first mention and simplified the terminology where appropriate (Lines 10–13). In addition, question-style sentences have been removed in accordance with the other reviewers’ suggestions
Comments 4: Abstract: The abstract is well structured but presents some limitations. Several acronyms (e.g., ICU, IC, HB, ESPEN, BEE) are used without definition, reducing clarity. The concept of “actual consumption” is not adequately specified. In addition, the results are partly unclear (e.g., correlations) and not sufficiently contextualized from a clinical perspective. Finally, the conclusions appear overstated considering the sample size and the lack of clinical outcomes.
Response 4:
In line with your suggestions, the abstract has been revised to improve clarity, consistency, and clinical relevance.All acronyms (ICU, IC, HB, ESPEN, BEE) are now defined at first mention. The concept of “actual consumption” has been clarified and replaced with “actual energy intake,” explicitly defined as the energy delivered to patients in clinical practice, and this definition has been added to the Methods section (Lines 204–205).The Results section has been revised to improve clarity while preserving the original findings, and brief interpretative statements have been incorporated to reflect their clinical relevance. In this context, the potential overestimation by predictive equations, the risk of underfeeding, and the limited agreement between methods have been briefly highlighted. In addition, the Conclusions section has been moderated to align with the sample size and cross-sectional design, avoiding overinterpretation.
We believe that these revisions have improved the clarity, transparency, and overall scientific balance of the abstract (Lines 23-51). Accordingly, the abstract has been restructured in line with the reviewers’ suggestions.
Comments 5: Introduction: The introduction is generally clear and well structured but presents some limitations. The research gap appears to be stated rather than critically supported; the claim that no studies exist on this topic is too strong and not adequately justified by references. A more cautious wording is recommended, along with better support from up-to-date literature. Additionally, some references are outdated (e.g., refs. 5 and 6), and more recent studies should be included to strengthen the scientific background.
Response 5:
The Introduction has been carefully revised in line with your suggestion. The research gap has been reformulated using a more balanced and critical perspective, and statements implying the absence of previous studies have been removed to avoid overgeneralization. Furthermore, recent and relevant literature has been incorporated to strengthen the scientific background of the manuscript. Although two references may be considered relatively older, they were retained based on the recommendations of the other reviewers. Overall, the Introduction has been substantially revised, and the necessary improvements have been implemented thanks to your valuable contribution.
Comments 6: Materials and Methods: This section presents several methodological issues that require clarification. First, the study design is not explicitly stated (e.g., prospective observational study), making it difficult to properly interpret the methodological framework. The sample size calculation is not adequately reported: key parameters are missing (e.g., “effect size of X” and “standard deviation of Y”), and the justification based on time, budget constraints, and the nature of a master’s thesis is not methodologically appropriate. The definition of “actual energy consumption” remains unclear: it is not specified whether this refers to prescribed, delivered, or effectively absorbed energy intake, despite being a central outcome of the study. Furthermore, the data collection process lacks transparency. Data were obtained from patient records, physicians, and relatives, but no information is provided on how consistency and reliability across these sources were ensured. The use of a 34-item questionnaire is reported; however, no details are provided regarding its validation, development, or psychometric properties, raising concerns about measurement validity. In addition, the sampling strategy is not clearly defined. Although the recruitment period (May–June 2023) is mentioned, it is not specified whether a consecutive, convenience, or other sampling approach was used, limiting the assessment of potential selection bias. Finally, the short observation period (three days, including the first 24–48 hours of ICU admission) may significantly affect the accuracy of energy estimations, given the metabolic instability typical of the acute phase. It is recommended to improve methodological clarity and transparency by explicitly stating the study design, completing the reporting of the sample size calculation, clearly defining key variables, and providing more detailed information on data collection procedures and sampling methods.
Response 6
The Materials and Methods section has been revised to improve clarity and methodological transparency.The study design has now been explicitly stated. The sample size calculation has been clarified by including the relevant statistical parameters, and non-methodological justifications have been removed. In addition, the definition of “actual energy intake” has been clearly specified in the Methods section.Data collection procedures have been described in more detail. Data were obtained from patient medical records and from one of the co-authors, who is the responsible physician in the intensive care unit. When necessary, missing or unclear information was verified through contact with patients’ relatives to ensure data completeness.The previously mentioned “34-item questionnaire” was not a validated scale but a structured form used to collect sociodemographic and clinical information. We apologize for this misleading terminology, and the text has been corrected accordingly. Therefore, no validity or reliability analysis was required. To avoid any potential misunderstanding, the term “questionnaire” has been removed from the manuscript and replaced with “structured data collection form (Line 167).”The sampling method has been clearly described in the revised manuscript. Finally, the limitations related to the short observation period have been explicitly acknowledged and discussed in the limitations section.
Comments 7:
Results: This section is overall rich in information but lacks clear structure and could be improved in terms of clarity of presentation. In particular, the results should be organized into thematic subsections to facilitate readability and interpretation. For example, it would be helpful to begin with a subsection describing participants’ characteristics (demographic and clinical), followed by a section on nutritional parameters, and finally the results of comparative and agreement analyses between methods (IC, HB, ESPEN). Currently, descriptive data, main findings, and advanced statistical analyses are presented sequentially but in a mixed manner, making it difficult to identify the key results of the study.
From a statistical perspective, several issues should be noted. In particular, a “negative correlation” is reported between IC and HB with r=0.35, which actually indicates a positive correlation, suggesting a potential error in the description of the results (lines 266–267). Moreover, the distinction between correlation and agreement is not always clearly addressed. While the use of Pearson correlation, Bland–Altman analysis, and Passing–Bablok regression is appropriate, the interpretation of these analyses appears partly unclear and redundant. Some information (e.g., biochemical parameters) is mentioned but not presented (“not presented”), reducing the transparency and verifiability of the data. Finally, the results are not adequately contextualized from a clinical perspective. For example, the approximately 500 kcal difference between measured and actual energy intake, although potentially relevant, is not discussed in terms of its clinical implications in critically ill patients.
Response 7:
We appreciate your careful evaluation of the Results section and have revised it accordingly to improve clarity and structureThe Results section has been reorganized using clear thematic subsections (participants’ characteristics, nutritional parameters, and comparative and agreement analyses) to enhance readability and facilitate interpretation. Mixed and potentially confusing expressions have been revised or removed, and the presentation of analyses and their corresponding results has been clarified and streamlined.We acknowledge and sincerely apologize for the error in reporting the correlation between IC and HB. This has been carefully corrected in the revised manuscript. In particular, a “negative correlation” is reported between IC and HB with r=0.35, which actually indicates a positive correlation, suggesting a potential error in the description of the results.Furthermore, the distinction between correlation and agreement analyses has been clarified, and redundant interpretations have been reduced to improve consistency and scientific accuracy.Regarding biochemical parameters, due to table limitations, these data could not be fully presented in tabular form. However, we have now clarified their presentation in the text to improve transparency.Finally, although the approximately 500 kcal difference between measured and actual energy intake represents a potentially important finding, its clinical implications have been more thoroughly discussed in the Discussion section, which has strengthened the overall interpretation of the study.
Comment 8:Discussion: The discussion addresses a clinically relevant topic but presents several issues in terms of interpretation and depth of analysis. First, the authors’ interpretations appear somewhat overly emphatic in relation to the available data. In particular, the emphasis on the use of indirect calorimetry as the preferred method is not fully supported, considering the small sample size, short observation period, and lack of relevant clinical outcomes. Moreover, the claim regarding the uniqueness of the study appears too strong and is not adequately supported by the existing literature, which already includes several studies comparing indirect calorimetry and predictive formulas. The discussion does not consistently maintain a clear distinction between the concepts of correlation and agreement, despite the use of appropriate statistical methods. This may lead to ambiguity in the interpretation of the results. In addition, the discrepancy between estimated energy requirements and actual intake, as highlighted in the results, is only partially discussed and not sufficiently explored in terms of its clinical and organizational implications, for example considering potential barriers to nutrition delivery in ICU settings. Finally, some parts are repetitive and redundant, reducing the overall clarity of the message.
Response 8: Dear Reviewer, we sincerely thank you for your careful reading and valuable comments. In line with your constructive suggestions, the Discussion section has been thoroughly revised.The interpretations have been moderated to avoid overly emphatic statements, and the findings are now presented in a more balanced and scientifically appropriate manner. The limitations of the study, including the relatively small sample size and short observation period, have been clearly acknowledged both in the Discussion and in a dedicated limitations section
In addition, the distinction between correlation and agreement analyses has been clarified, and the results have been interpreted more explicitly in the context of the applied statistical methods. The discussion has been further strengthened by integrating up-to-date literature to support and contextualize the findings.The discrepancy between estimated energy requirements and actual energy intake has been more comprehensively explored, including its potential clinical and organizational implications in ICU settings.Finally, repetitive and redundant statements have been removed, and the overall structure and flow of the Discussion have been improved to enhance clarity and readability.
Comments 9: Conclusion: The concluding section presents some issues in terms of both structure and content. First, it would be preferable to present the limitations section before the conclusions, in order to provide a more balanced and contextualized interpretation of the findings. Although some limitations are acknowledged (small sample size, measurements performed within the first 24–48 hours, and population heterogeneity), they are not comprehensively discussed. In particular, important aspects such as the lack of clinical outcomes, potential bias related to the measurement of actual intake, and the single-center nature of the study are not adequately addressed. Furthermore, the conclusions appear somewhat overstated in relation to the available data. The emphasis on the use of indirect calorimetry and the related clinical recommendations are not fully supported, given the study design and its limitations. Overall, it is recommended to reorganize this section by presenting the limitations first and revising the conclusions in a more cautious manner, in line with the study findings.
Response 9:
In line with your suggestions, this section has been carefully revised.First, as recommended, the limitations of the study have been presented under a separate heading placed before the Conclusion section, at the end of the Discussion. These include key aspects such as the relatively small sample size, the short observation period covering the first 24–48 hours of ICU admission, the heterogeneous nature of the study population, the lack of clinical outcome data, potential bias related to the measurement of actual energy intake, and the single-center design of the study.In addition, the Conclusion section has been revised using a more cautious and balanced tone, avoiding overly strong or unsupported statements. The interpretation of the findings has been aligned more closely with the study design and its limitations. The emphasis on indirect calorimetry has been moderated, and clinical implications are now presented in a more appropriate and realistic context.Furthermore, the conclusions have been reorganized to better reflect the main findings of the study without overgeneralization. The discrepancy between estimated energy requirements and actual energy intake has been interpreted more clearly, and the roles of predictive equations and indirect calorimetry have been discussed in a more balanced manner.Overall, the Conclusion section has been revised to improve clarity, scientific accuracy, and consistency with the presented results and acknowledged limitations.
Comments 10: Tables: The tables and figures present several issues that affect clarity and interpretability. First, the tables are not self-contained: several acronyms (e.g., APACHE II, SOFA, mNUTRIC, PNI, IC, HB) are not defined within the table footnotes but only in the final abbreviations section. This limits readability and does not align with standard reporting practices. Additionally, some tables lack structural clarity. Table 2 mixes different data presentation formats (mean ± standard deviation and median with interquartile ranges) without a clear distinction. Table 3 has a complex and difficult-to-interpret layout, while Table 4 includes an incomplete title and a non-intuitive structure. There are also inconsistencies in numerical formatting (use of commas vs decimal points) and non-uniform reporting of measurement units.
Response 10: In line with your suggestions, all tables and figures have been carefully revised and corrected.The design, formatting, footnotes, and presentation of all tables have been improved to ensure clarity, consistency, and compliance with standard reporting practices. All abbreviations (e.g., APACHE II, SOFA, mNUTRIC, PNI, IC, HB) are now clearly defined in the table footnotes, and data presentation formats have been standardized across all tables. In addition, table structures have been reorganized to enhance readability and interpretability, and all titles have been completed and clarified.Furthermore, to ensure optimal presentation quality and full compliance with the journal’s formatting requirements, professional support was obtained from the MDPI Table Editing Service. As part of this process, both tables and figures were revised, including improvements in layout, formatting, and graphical resolution.Overall, these revisions have significantly improved the clarity, visual quality, and journal compliance of the tables and figures.
Comments 11: Figures: Figure 1 appears visually dense and combines multiple analyses within a single panel without sufficiently clear labeling. Figure 2 (flow diagram) is overly simplified and could be improved to better align with reporting standards (e.g., STROBE).
Response 11:
In line with your suggestions, both Figure 1 and Figure 2 have been revised to improve clarity and presentation quality. Figure 1 has been reorganized to reduce visual density, with clearer labeling and improved structure to facilitate interpretation of the presented analyses.Figure 2 (flow diagram) was first revised by the authors to ensure alignment with STROBE reporting standards. Subsequently, both figures were further refined with the support of the MDPI Table Editing Service, including improvements in layout, formatting, and overall visual quality.
These revisions have enhanced the clarity, interpretability, and reporting quality of the figures.
Author Response File: 
Author Response.docx
Reviewer 2 Report
Comments and Suggestions for Authors
The manuscript addresses an important clinical issue in critically ill patient nutrition, namely the accuracy of methods for estimating energy requirements in intensive care. The comparison between indirect calorimetry (IC) and predictive formulas (Harris-Benedict, ESPEN) is relevant and of practical interest. The manuscript is well-structured; However, several points need consideration:
- Title: long, needs reformulation
- Abstract: Methodology is insufficiently detailed
Critical omissions:
Sample size
Patient characteristics (ventilation? sepsis?)
Time of measurements (acute phase?)
IC protocol
Patient nutritional status
- Introduction: The term “actual consumption” is central to your study but is never clearly defined in the introduction. It is essential to specify whether this refers to the prescribed, administered, or actually absorbed intake.
Inconsistency and Repetition of the Scientific Message
The concepts of malnutrition, complications, and energy imbalance are repeated several times without providing new information, which hinders readability and scientific impact.
Lack of Clear Statement of the Scientific Gap
You mention that the data are limited, but you do not clearly specify:
what is missing from the literature
why your study is necessary
The gap must be explicitly stated.
Poorly Positioned and Redundant Study Objective
The objective appears late (end of the text) and is repeated in several forms. It should be stated only once, concisely and precisely.
Lack of Logical Structure
The introduction does not follow a clear progression (context → problem → limitations → objective). The ideas are presented in a fragmented manner.
Unbalanced Presentation of Methods (CI vs. Formulas)
Indirect calorimetry is presented as the reference method without sufficient critical discussion of its limitations (cost, feasibility, accessibility), which introduces bias.
- Vague definition of “actual consumption”
Central concept of the study not clearly defined:
prescribed intake?
actually administered intake?
absorbed intake?
- Methodology
The type of study is not clearly stated:
observational? prospective? cross-sectional?
Conceptual problem: biased comparison
You are comparing estimated energy requirements
vs. actual consumption; however, consumption depends on digestive tolerance, nutritional interruptions, and clinical practices.
- Overinterpretation of results
- Conclusion:
The conclusion is too descriptive and insufficiently concise.
Author Response
Dear Reviewer,
We sincerely thank you for your valuable contributions and constructive suggestions. In line with your comments and the revised flow of the manuscript, the necessary revisions have been made and the overall structure has been improved. All modifications and additions have been clearly marked in red throughout the text.
Response to Reviewer #2:
Comments 1: Title: long, needs reformulation
Response 1:
The manuscript title has been shortened and revised in accordance with the reviewers’ valuable suggestions as “Accuracy of Predictive Formulas vs. Indirect Calorimetry in Estimating Energy Needs of Intensive Care Unit Patients.”
Comments 2: Abstract: Methodology is insufficiently detailed Critical omissions: Sample size Patient characteristics (ventilation? sepsis?) Time of measurements (acute phase?) IC protocol Patient nutritional status
Response 2:
In line with your suggestions, the methodology section has been revised to improve clarity and completeness. The sample size has been explicitly stated, and patient characteristics, including mechanical ventilation status, have been clearly defined. In addition, the timing of measurements (acute phase), the indirect calorimetry (IC) protocol, and the assessment of patients’ nutritional status (PNI and mNUTRIC) have been more clearly described.
Comments 3: Introduction: The term “actual consumption” is central to your study but is never clearly defined in the introduction. It is essential to specify whether this refers to the prescribed, administered, or actually absorbed intake.
Response 3:
In line with the reviewers’ suggestions, the concept of “actual energy intake” has been clearly defined in the Methods section to avoid ambiguity and ensure consistency throughout the manuscript. Specifically, “In this study, ‘energy intake’ refers to the energy actually delivered to patients in clinical practice, rather than prescribed or theoretically calculated values.” (Line 204-205)
Comments 4: The concepts of malnutrition, complications, and energy imbalance are repeated several times without providing new information, which hinders readability and scientific impact.
Response 4:
In response, we have carefully revised the manuscript to remove repetitive statements regarding malnutrition, complications, and energy imbalance. The relevant sections have been consolidated and rewritten to present the information clearly and concisely, improving both readability and scientific impact.
Comments 5: Inconsistency and Repetition of the Scientific Message.Lack of Clear Statement of the Scientific Gap,
Response 5:
In line with your suggestions, the manuscript has been revised to improve consistency and reduce repetition in the scientific message.The study has been restructured using a more critical and balanced perspective, supported by up-to-date literature. The research gap has been more clearly defined, and the study objectives as well as its contribution to the existing literature have been explicitly stated.In addition, the limitations of the study have been clearly identified and discussed. The Introduction, Discussion, Limitations, and Conclusion sections have been thoroughly revised, and additional clarifications have been incorporated to improve clarity, coherence, and scientific rigor throughout the manuscript.
Comments 6: You mention that the data are limited, but you do not clearly specify:
what is missing from the literatüre,why your study is necessary,The gap must be explicitly stated.Poorly Positioned and Redundant Study Objective.The objective appears late (end of the text) and is repeated in several forms. It should be stated only once, concisely and precisely.
Response 6:
As previously stated, the manuscript has been comprehensively revised in line with your suggestions. Repetitive expressions have been simplified, the scientific message has been strengthened, and the study has been restructured using a more critical perspective supported by up-to-date literature.
The research gap, study objectives, and contribution to the literature have been clarified. In addition, the Introduction, Discussion, Limitations, and Conclusion sections have been revised to improve clarity, coherence, and overall flow.
Comments 7: Lack of Logical Structure
The introduction does not follow a clear progression (context → problem → limitations → objective). The ideas are presented in a fragmented manner.
Unbalanced Presentation of Methods (CI vs. Formulas)
Indirect calorimetry is presented as the reference method without sufficient critical discussion of its limitations (cost, feasibility, accessibility), which introduces bias.
Response 7:
You are absolutely right, and the Introduction section has been revised to ensure a clear and logical flow (context → problem → limitations → objective).While indirect calorimetry (IC) is widely described as the gold standard in the literature, and similar expressions are commonly used in many studies including those cited in our manuscript, we acknowledge that our previous wording may have unintentionally introduced a potential bias. We sincerely apologize for this lack of clarity.Accordingly, the text has been revised to present a more balanced and neutral perspective. The limitations of IC, including issues related to cost, feasibility, and accessibility, have now been explicitly addressed to avoid any potential bias and to provide a more comprehensive and objective representation of the literature.In addition, these considerations have been consistently incorporated not only in the Introduction but also in the Discussion, Limitations, and Conclusion sections to ensure coherence and consistency throughout the manuscript.
Comments 8: - Vague definition of “actual consumption”
Central concept of the study not clearly defined:
prescribed intake?
actually administered intake?
absorbed intake?
Response 8:
In line with your suggestion, the definition of “actual energy intake” has been clearly specified in the Methods section to eliminate any ambiguity.
Specifically, “In this study, ‘energy intake’ refers to the energy actually delivered to patients in clinical practice, rather than prescribed or theoretically calculated values.”
Comments 9: - Methodology.The type of study is not clearly stated:
observational? prospective? cross-sectional?
Response 9:
We thank the reviewer for this comment. The study is a cross-sectional observational study in which surveys and scales were applied to patients hospitalized in the intensive care unit (ICU) and collected at a single time point. This clarification has been added to the Methods section of the revised manuscript. (Line 131).
Comments 10: Conceptual problem: biased comparison
You are comparing estimated energy requirements vs. actual consumption; however, consumption depends on digestive tolerance, nutritional interruptions, and clinical practices.
Response 10:
In line with your suggestions, relevant points have been emphasized throughout the manuscript from the Introduction to the Conclusion in accordance with the current literature and in a coherent manner.
We fully understood your concern and recognized that, while attempting to reflect the literature, some of our expressions may have been perceived as overly emphatic and potentially misleading. We sincerely apologize for this and have revised all such statements to ensure a more balanced, accurate, and neutral presentation of the findings.
Comments 11: The conclusion is too descriptive and insufficiently concise.
Response 11:
The Conclusion section has been revised in line with your suggestion to improve conciseness and clarity.
Reviewer 3 Report
Comments and Suggestions for Authors
Which Method is Closer to the Actual Food Consumption of Intensive Care Unit Patients: Indirect Calorimetry and Formulas and How Compatible Are They with Each Other?
Comment 1. The authors are asked to revised the title to remove the question mark and combine the two phrases into a single title.
The authors may write as
Accuracy of Predictive Formulas vs. Indirect Calorimetry in Estimating Energy Needs of Intensive Care Unit Patients
Comment 2. The authors are instructed to remove the questions from highlights part. Authors have to write the overall findings of the study briefly using bullets.
Comment 3. The authors used the terminology “Bland-Atman Analysis” in the keywords section; however, they do not explain any idea about this term in the abstract section. So, the authors have to write brief information about “Bland-Atman Analysis” in abstract 1st and then used this term.
Comment 4. At line 99 the authors used the terminology “FiO2”. What is “FiO2”? Mention it 1st then used it.
Comment 5. The authors have to explain how do predictive formulas (such as Harris-Benedict and ESPEN) compare to indirect calorimetry in determining energy requirements?
Comment 6. At line 120 the authors mentioned “K…. C…. H….”. Please mention the full name of hospital 1st then used its proper abbreviation format. (K…. C…. H) this in not a proper form of writing, you can write like this “KCH”.
Same patter followed by the authors at line 136 (N… N… Y…). please correct this format.
Comment 7. Given its potential advantages, can indirect calorimetry be used more frequently in clinical practice? Explain it briefly.
Comment 8. Line 133-135 (“Although an increased number of participants could be beneficial, the fact that this study is a master’s thesis project, time constraints, and the project support budget have influenced the final sample size.”)
The authors are instructed to move this section (Line 133-135) to the limitation part instead of methodology part.
Comment 9. Before “2.1. Study Plan and Sample Selection”, the authors are suggested to incorporate a point as “Study Area” (In this point the authors have to write from which areas of your country or from another country or from which hospitals or health care centres they select the experimental samples).
Comment 10. The authors should explain briefly the inclusion and exclusion criteria for participants in this study.
Comment 11. Line 252, what do you mean by NG and PEG? The authors used lots of terminology in this article but they have to introduce the terminology 1st at the text where they used it 1st and then followed the terminology throughout the article.
Example: 1st the authors have to write like this, Nasogastric (NG) in a respective line.
After 1st introduce, they can write it as NG throughout the article.
Please followed this instruction properly.
Comment 12. Ensure that all the terminology with proper full form listed in the abbreviations list of the article.
Comment 13. There are no real discussion of the results and no comparisons with data reported in the literature. This is not fine. Discussion of the results are always compulsory.
Comment 14. Limitations of the study mark as point 7. After that mention the patents in next point.
Comment 15. “Fig2. Flow Diagram” Write this figure caption properly and explain briefly what this figure wants to reflect.
Comment 16. At the methodology part the authors write the equation as follows:
Harris Benedict Formula: 217 Man=66,473+(13,7516x W) + (5,0033xH) -(6,755xA) 218 Woman=655,0955+(9,5634xW) +(1,8496xH) (4,6756xA)
Where as the actual equation are
Male:
BEE (kcal/day) = 66.47 + (13.75 x weight in kg) + (5.003 x height in cm) - (6.755 x age in years)
Female:
BEE (kcal/day) = 655.1 + (9.563 x weight in kg) + (1.85 x height in cm) - (4.676 x age in years)
Now the main thing is (,) coma and (.) point these two things are not same. So why the authors used (,) coma in Benedict equation, please clarify it.
Same problem noted in Table 2. Please clarify it. [Concept of (,) coma and (.) point].
Comment 17. What strategies can be used in this study to optimize energy intake and reduce malnutrition in critically ill patients?
Comment 18. What future research is needed to develop more accurate and practical methods for determining energy requirements in ICU patients? Please clarify it briefly.
Comment 19. What are the main outcomes of this study?
Comment 20. Mark the each and every point and subpoint very carefully.
Example.
2.5. Calculation of Basal Energy Expenditure
2.5.1. Indirect Calorimetry Protocol
2.5.3. Formula Protocol (This subpoint will be mark as 2.5.2)
The authors are instructed to correct it.
Comment 21. The authors are suggested to rewrite “ 2.5.3. Formula Protocol” part carefully. (Line 210-214) Don’t use unnecessary questions mark, write simple sentences that are easy to understand.
Comment 22. In some places authors write as “Figure 1” and in other places write as “Fig 1”. Authors are suggested to use any one format (Figure 1 or Fig 1) throughout the manuscript.
Comment 23. Rewrite the caption of Table 1 and Table 2. Present captions are not informative and clear. Please write it clearly and briefly that what types of result reflected by the Table 1, Table 2.
Comment 24. The authors are instructed to incorporated the SD values in Table 2 and Table 3.
Example: Mean ± SD/Median (25-75%), following this format.
Comment 25.
Why this table embedded after Table 4. The table is not clear and all the information in this table are not readable. The authors are requested to clarify it. If this table is related with the manuscript, mark it properly with proper table number and relatable table caption.
Comment 26. The authors are asked to clarify what they mean by “95% limit of ag”, which mentioned in Fig.1.
Is this line being incomplete?
Fig.1 The correlation and agreement between different measurements for basal energy expenditure and the reference indirect calorimetry measurement. a Scatter plot with Pearson correlation analysis. The red color line showed a linear regression curve, where the light-red band represented the 95% confidence interval b Bland-Altman analysis. A horizontal solid line corresponds to the estimated bias, while two horizontal dash lines represent the upper and lower prediction limits, corresponding to the 95% limit of ag
Comment 27. Fig 2 is not visible properly. Authors are instructed to enhance the resolution of the picture.
Comment 28. Make sure the manuscript contains accurate citations for all of the sources. DOI no maintain is mandatory for all the references. Rearrange the references properly.
Author Response
Dear Reviewer,
We sincerely thank you for your valuable contributions and constructive suggestions. In line with your comments and the revised flow of the manuscript, the necessary revisions have been made and the overall structure has been improved. All modifications and additions have been clearly marked in red throughout the text.
Response to Reviewer #3:
Comments 1: The authors are asked to revised the title to remove the question mark and combine the two phrases into a single title. The authors may write as:Accuracy of Predictive Formulas vs. Indirect Calorimetry in Estimating Energy Needs of Intensive Care Unit Patients
Response 1: We thank the reviewer for this suggestion. The title has been revised according to your recommendation: the question mark has been removed, and the two phrases have been combined into a single, concise title. The revised title now reads: “Accuracy of Predictive Formulas vs. Indirect Calorimetry in Estimating Energy Needs of Intensive Care Unit Patients.”
Comments 2: The authors are instructed to remove the questions from highlights part. Authors have to write the overall findings of the study briefly using bullets.
Response 2: All question statements have been removed, and the section has been revised in accordance with the reviewer’s suggestions.
Comments 3: The authors used the terminology “Bland-Atman Analysis” in the keywords section; however, they do not explain any idea about this term in the abstract section. So, the authors have to write brief information about “Bland-Atman Analysis” in abstract 1st and then used this term.
Response 3: We thank the reviewer for this valuable comment. In response, we have added a brief explanation of the Bland-Altman analysis in the Materials and Methods section. The sentence now reads: “Agreement between IC and predictive formulas was assessed using Bland-Altman analysis, a statistical method that evaluates agreement between two measurement techniques.” This addition clarifies the use of the term and addresses the reviewer’s concern regarding its absence in the abstract and methods section.
Comments 4: At line 99 the authors used the terminology “FiO2”. What is “FiO2”? Mention it 1st then used it.
Response 4: We thank the reviewer for this comment. The terminology “FiOâ‚‚” has now been explained at its first occurrence in the Materials and Methods section. The sentence now reads: “Fraction of inspired oxygen (FiOâ‚‚) was recorded during mechanical ventilation.” This clarification ensures that readers understand the term before it is used throughout the manuscript. This change can be found in the revised manuscript on Line 156.
Comments 5: The authors have to explain how do predictive formulas (such as Harris-Benedict and ESPEN) compare to indirect calorimetry in determining energy requirements?
Response 5:
The comparison between energy requirements estimated by predictive formulas (Harris–Benedict, ESPEN) and those measured by indirect calorimetry (IC) has now been clearly described in the Statistical Analysis subsection of the Methods section. Specifically, the relationship between basal energy expenditure (BEE) values obtained by different methods was evaluated using Pearson correlation analysis, while agreement between methods was assessed using Bland–Altman analysis and Passing–Bablok regression. This revision clarifies both the methodological approach and how the comparison was performed. This change can be found in the revised manuscript on Page 7, Lines 262-266.
Comments 6: At line 120 the authors mentioned “K…. C…. H….”. Please mention the full name of hospital 1st then used its proper abbreviation format. (K…. C…. H) this in not a proper form of writing, you can write like this “KCH”. Same patter followed by the authors at line 136 (N… N… Y…). please correct this format.
Response 6: We thank the reviewer for this comment. Due to anonymization during the initial draft, the hospital names were written as “K…. C…. H…” and “N…. N…. Y… U…”. In the revised manuscript, the full names have now been provided at their first occurrences as “Kayseri City Hospital (KCH)” and “Nuh Naci Yazgan University (NNYU)”, and the abbreviations KCH and NNYU are used thereafter throughout the text. This change can be found in the revised manuscript on Line 147 and 150 Page 4.
Comments 7: Given its potential advantages, can indirect calorimetry be used more frequently in clinical practice? Explain it briefly.
Response 7:
We thank the reviewer for this comment. Although indirect calorimetry (IC) is considered the reference method for measuring energy expenditure, its routine use in clinical practice is limited due to high cost, the need for specialized equipment and trained personnel, and potential interference from clinical conditions such as high FiOâ‚‚ levels, ventilator settings, and hemodynamic instability. Therefore, while IC provides accurate assessment and may be prioritized for high-risk patients, its widespread use remains constrained. In addition, although IC is still regarded as the gold standard in the literature, its use in routine practice is limited by these factors. This issue has been comprehensively addressed in the Introduction, Discussion, Conclusion, and Limitations sections of our manuscript, supported by up-to-date literature, and a clearer, more balanced message aligned with the aim of our study has been provided. This change can be found in the revised manuscript on Page 9–10, Lines 408-411”
Comments 8: Line 133-135 (“Although an increased number of participants could be beneficial, the fact that this study is a master’s thesis project, time constraints, and the project support budget have influenced the final sample size.”)
The authors are instructed to move this section (Line 133-135) to the limitation part instead of methodology part.
Response 8:
The statement regarding the sample size has been moved from the Materials and Methods section to the Limitations section, as suggested. The sentence has also been revised as follows: “Although the sample size was considered adequate based on power analysis, it was conducted as part of a master’s thesis and was subject to time and budget constraints, which may have limited the statistical power of the study.” This change can be found in the revised manuscript on Page 10, Lines 398-401.
Comments 9: Before “2.1. Study Plan and Sample Selection”, the authors are suggested to incorporate a point as “Study Area” (In this point the authors have to write from which areas of your country or from another country or from which hospitals or health care centres they select the experimental samples).
Response 9:
We thank the reviewer for this comment. As suggested, a “Study Area” section has been added before “2.1. Study Plan and Sample Selection,” in which we clearly describe from which city and hospitals the study samples were selected. This change can be found in the revised manuscript on Line 126-129, Page 3.
Comments 10: The authors should explain briefly the inclusion and exclusion criteria for participants in this study.
Response 10:
The inclusion and exclusion criteria are clearly described in the Materials and Methods section of the manuscript. The relevant statements are provided below as written in the manuscript:
“Patients were included in the study if they were intubated or undergoing mechanical ventilation via tracheostomy in the last 24 hours or longer, aged 18 and above, and showed no significant changes in mechanical ventilation parameters (FiOâ‚‚, airway pressure, respiratory rate, minute ventilation) during the periods when IC measurements were taken. Fraction of inspired oxygen (FiOâ‚‚) was recorded during mechanical ventilation. Patients were excluded if they required FiOâ‚‚>0.6 mmHg and PEEP ≥20 cm/Hâ‚‚O, were hyperthermic (>38°C) or hypothermic (<35°C), had amputated extremities, suffered air leaks in any of the respiratory circuits, had an RQ ratio outside the physiological limits (0.7–1.2), were non-compliant with mechanical ventilation, or had any condition that could affect the measurement.”This clarification can be found in the revised manuscript on Page 4, Lines 152-161.
Comments 11: Line 252, what do you mean by NG and PEG? The authors used lots of terminology in this article but they have to introduce the terminology 1st at the text where they used it 1st and then followed the terminology throughout the article.
Example: 1st the authors have to write like this, Nasogastric (NG) in a respective line. After 1st introduce, they can write it as NG throughout the article. Please followed this instruction properly.
Response 11:
We thank the reviewer for this comment. All abbreviations, including NG (Nasogastric) and PEG (Percutaneous Endoscopic Gastrostomy), have now been introduced at their first occurrence in the text, and the abbreviations are used consistently throughout the manuscript thereafter. This change can be found in the revised manuscript on Line 271-272 Page 7.
Comments 12: Ensure that all the terminology with proper full form listed in the abbreviations list of the article.
Response 12:
All abbreviations used in the manuscript are now listed with their full forms in the Abbreviations section, and each abbreviation is introduced at its first occurrence in the text.
Comments 13: There are no real discussion of the results and no comparisons with data reported in the literature. This is not fine. Discussion of the results are always compulsory.
Response 13:
In accordance with the reviewer’s suggestion, the Discussion section has been thoroughly revised. The findings have been compared with the existing literature and further elaborated to enhance the scientific interpretation.
Comments 14: Limitations of the study mark as point 7. After that mention the patents in next point.
Response 14:
We thank the reviewer for this valuable suggestion. The limitations have been clearly outlined as a separate paragraph at the end of the Discussion section. However, due to journal requirements and in consideration of other reviewers’ comments, it was not feasible to present them as a numbered section (e.g., point 7). Nonetheless, the limitations are now explicitly and clearly stated in a dedicated paragraph immediately preceding the Conclusion.
Comments 15: “Fig2. Flow Diagram” Write this figure caption properly and explain briefly what this figure wants to reflect.
Response 15:
We thank the reviewer for this valuable comment. Figure 2 (flow diagram) has been comprehensively revised in accordance with the STROBE guidelines, both in terms of content and visual presentation, through collaboration between the authors and the MDPI Table Editing Service. The revised version presents the patient selection and study workflow in a clearer, more systematic, and transparent manner. Specifically, the figure illustrates the inclusion of 38 mechanically ventilated ICU patients from seven units, the data collection process, scoring systems (SOFA, APACHE II, mNUTRIC, PNI), 24-hour dietary records, energy calculations (IC, HB, and ESPEN), and the statistical analyses performed (correlation, Bland–Altman agreement, and Passing–Bablok regression). This revision has significantly improved the clarity and methodological transparency of the figure.
Comments 16: At the methodology part the authors write the equation as follows:
Harris Benedict Formula: 217 Man=66,473+(13,7516x W) + (5,0033xH) -(6,755xA) 218 Woman=655,0955+(9,5634xW) +(1,8496xH) (4,6756xA)
Where as the actual equation are
Male:
BEE (kcal/day) = 66.47 + (13.75 x weight in kg) + (5.003 x height in cm) - (6.755 x age in years)
Female:
BEE (kcal/day) = 655.1 + (9.563 x weight in kg) + (1.85 x height in cm) - (4.676 x age in years)
Now the main thing is (,) coma and (.) point these two things are not same. So why the authors used (,) coma in Benedict equation, please clarify it.
Same problem noted in Table 2. Please clarify it. [Concept of (,) coma and (.) point].
Response 16:
We thank the reviewer for this important comment. The Harris–Benedict equations have been revised and rewritten in the correct format in line with your suggestion. The incorrect use of commas (,) as decimal separators has been corrected, and dots (.) have been used in accordance with international scientific writing conventions. The same corrections have also been applied to Table 2. This revision ensures the accuracy of numerical expressions and consistency throughout the manuscript.
Comments 17: What strategies can be used in this study to optimize energy intake and reduce malnutrition in critically ill patients?
Response 17:
Based on our study findings, several strategies can be proposed to optimize energy intake and reduce malnutrition in critically ill patients. These include individualized assessment of energy requirements (using indirect calorimetry whenever available), careful and appropriate use of predictive equations, and close monitoring of delivered energy with adjustments according to the patient’s clinical condition. In addition, clinical factors such as feeding interruptions, gastrointestinal intolerance, and hemodynamic instability should be taken into account, and nutritional plans should be adapted accordingly. Furthermore, the involvement of dietitians or nutrition specialists in ICU teams may improve the accuracy of nutritional planning, enhance monitoring of energy delivery, and support timely adjustments in response to clinical changes.
In line with your suggestion, these strategies have also been incorporated into the relevant paragraph in the Discussion section to further strengthen the clinical implications of our findings.
Comments 18: What future research is needed to develop more accurate and practical methods for determining energy requirements in ICU patients? Please clarify it briefly.
Response 18:
We thank the reviewer for this important comment. Based on our study findings, several strategies can be proposed to optimize energy intake and reduce malnutrition in critically ill patients. These include individualized assessment of energy requirements (using indirect calorimetry whenever available), close monitoring of nutritional intake and digestive tolerance, implementation of standardized ICU nutrition protocols, involvement of nutrition specialists, and minimizing interruptions in nutritional support whenever possible.
Regarding future research, there is a clear need for larger, multicenter studies with extended follow-up periods to validate predictive equations against indirect calorimetry across diverse ICU populations. In addition, the development of practical bedside tools for dynamic estimation of energy requirements, further investigation of patient-specific factors influencing energy needs, and evaluation of combined approaches (indirect calorimetry and predictive formulas) on clinical outcomes are warranted.
These aspects have also been addressed in the manuscript. Specifically, in the Limitations section, the single-center design, limited sample size, and absence of longitudinal follow-up are acknowledged, highlighting the need for larger and long-term studies. Furthermore, in the Discussion and Conclusion sections, the clinical applicability of indirect calorimetry, the limitations of predictive equations, and the importance of monitoring delivered energy are emphasized, supporting the need for future research in this field.
Comments 19: What are the main outcomes of this study?
Response 19:
Our study compared the estimation of energy requirements in mechanically ventilated ICU patients using predictive formulas (Harris–Benedict and ESPEN) with measurements obtained via indirect calorimetry (IC). The main findings are as follows:
Limited agreement between predictive formulas and IC: Estimated energy requirements differed from IC measurements, highlighting individual variability in patients’ metabolic needs.
Actual energy intake was lower than predicted: Patients’ energy intake was frequently below the values suggested by both Harris–Benedict and ESPEN formulas, indicating the risk of overestimation if relying solely on predictive formulas.
Importance of individualized monitoring: IC measurements provide a more accurate assessment of energy expenditure and help optimize nutritional support in critically ill patients.
In conclusion, our study emphasizes that relying solely on predictive formulas may not accurately reflect patients’ energy needs. Individualized monitoring, particularly using IC when available, is crucial to ensure precise nutritional support in ICU patients. Our study also has some limitations, which have been outlined in the manuscript.
Comments 20: Mark the each and every point and subpoint very carefully.
Example.
2.5. Calculation of Basal Energy Expenditure
2.5.1. Indirect Calorimetry Protocol
2.5.3. Formula Protocol (This subpoint will be mark as 2.5.2)
The authors are instructed to correct it.
Response 20:
All main headings and subheadings have been carefully revised and numbered in a consistent and sequential manner.
Comments 21: The authors are suggested to rewrite “ 2.5.3. Formula Protocol” part carefully. (Line 210-214) Don’t use unnecessary questions mark, write simple sentences that are easy to understand.
Response 21:
As suggested, we have carefully rewritten the “2.5.3. Formula Protocol” section using simple and clear sentences, removing unnecessary question marks. With this correction, the section is now easier to read and understand. This change can be found in the revised manuscript on Line 227-228, Page 6.
Comments 22: In some places authors write as “Figure 1” and in other places write as “Fig 1”. Authors are suggested to use any one format (Figure 1 or Fig 1) throughout the manuscript.
Response 22: Dear Reviewer,Thank you for your valuable comment. As you pointed out, “Figure 1” and “Fig 1” were used inconsistently in the manuscript. We have revised the manuscript to use a single format consistently throughout and the reference to “Figure 2” has also been corrected. This change can be found in the revised manuscript.
Comments 23: Rewrite the caption of Table 1 and Table 2. Present captions are not informative and clear. Please write it clearly and briefly that what types of result reflected by the Table 1, Table 2.
Response 23:
The table captions and table layouts have been revised.
Comments 24: The authors are instructed to incorporated the SD values in Table 2 and Table 3. Example: Mean ± SD/Median (25-75%), following this format.
Response 24:
The tables have been revised to present the data more clearly in line with your suggestion. They were first reorganized by the authors and subsequently reviewed and finalized by the MDPI Table Editing Service. Variables with normal distribution are presented as Mean ± SD, while non-normally distributed variables are presented as Median (25–75%). Therefore, standard deviation (SD) values are provided only for normally distributed variables. The use of “/” in the tables indicates which format (Mean ± SD or Median (25–75%)) has been applied depending on the distribution of the variable. In addition, this approach has been clearly stated in the table footnotes (e.g., “Data are not normally distributed, Median (25–75%) is used. For p value tested using a Kruskal–Wallis.”). This format has been applied consistently in Table 2 and Table 3.
Comments 25: Why this table embedded after Table 4. The table is not clear and all the information in this table are not readable. The authors are requested to clarify it. If this table is related with the manuscript, mark it properly with proper table number and relatable table caption.
Response 25:
Table 5 has been included to provide the numerical counterpart of the correlation and Bland–Altman analyses presented in Figure 1. This table summarizes the comparison of energy requirements obtained using different methods (indirect calorimetry [IC], Harris–Benedict, and ESPEN) and evaluates the agreement between these methods. Specifically, Passing–Bablok regression analysis was used to assess systematic and proportional errors, while ICC (intraclass correlation coefficient) and CCC (concordance correlation coefficient) were used to evaluate agreement and consistency between methods. While Figure 1 presents these relationships graphically, Table 5 provides a more detailed numerical and statistical summary of the findings. In line with your suggestion, the table has been properly revised, assigned as Table 5, and presented with a clear and informative caption. In addition, the table was further improved in accordance with the recommendations of the MDPI Table Editing Service to enhance formatting, clarity, and readability.
Comments 26: The authors are asked to clarify what they mean by “95% limit of ag”, which mentioned in Fig.1.
Is this line being incomplete?
Fig.1 The correlation and agreement between different measurements for basal energy expenditure and the reference indirect calorimetry measurement. a Scatter plot with Pearson correlation analysis. The red color line showed a linear regression curve, where the light-red band represented the 95% confidence interval b Bland-Altman analysis. A horizontal solid line corresponds to the estimated bias, while two horizontal dash lines represent the upper and lower prediction limits, corresponding to the 95% limit of ag
Response 26:
Thank you for your valuable comment. We apologize for the unclear notation. The term “95% limit of ag” in Fig. 1 is a typographical error. It should read “95% limits of agreement”, which corresponds to the upper and lower prediction limits in the Bland-Altman analysis. This has now been corrected in the figure caption to clarify the meaning.
Comments 27: Fig 2 is not visible properly. Authors are instructed to enhance the resolution of the picture.
Response 27:
All figures and graphs, including Figure 2, have been revised and improved in terms of clarity and resolution with the support of the MDPI Table Editing Service In a similar study conducted by Anne-Françoise Rousseau et al., titled “Measured Energy Expenditure Using Indirect Calorimetry in Post-Intensive Care Unit Hospitalized Survivors: A Comparison with Predictive Equations,” the Bland–Altman analysis was presented in a figure format similar to ours, and the other statistical analyses were also visualized using comparable methods.
Comments 28: Make sure the manuscript contains accurate citations for all of the sources. DOI no maintain is mandatory for all the references. Rearrange the references properly.
Response 28:
All references have been carefully reviewed, in-text citations have been verified, and the reference list has been rearranged accordingly. In addition, DOI numbers have been added for all references where available. These revisions ensure the accuracy and consistency of the reference section.
Round 2
Reviewer 1 Report
Comments and Suggestions for Authors
The authors have made a good effort in revising the manuscript, with evident improvements compared to the previous version. In particular, the introduction is now clearer and better structured, the study rationale is more explicitly presented, and the methods section appears more robust, thanks to a more detailed description of the sampling strategy and statistical analysis. The discussion has also been expanded and is better contextualized within the existing literature.
The study addresses a clinically relevant topic, highlighting the discrepancy between estimated energy requirements and actual energy intake in critically ill patients. The comparison between indirect calorimetry and predictive formulas, combined with real-world clinical data, represents a valuable contribution to the field of clinical nutrition in intensive care.
However, some issues still need to be addressed before the manuscript can be considered for publication:
- Study design: The manuscript refers to the study as both “prospective” and “cross-sectional observational,” creating methodological ambiguity. The study design should be clearly and consistently defined throughout the manuscript. In addition, some redundancy should be avoided (e.g., repeated reporting of the sample size). Please revise for clarity and consistency (lines 125–134)
- Lack of clinical outcomes: Although the study provides useful insights into discrepancies between estimated and delivered energy, it does not include relevant clinical outcomes (e.g., mortality, length of stay, complications). This limits the clinical applicability of the findings. The authors are encouraged to more explicitly acknowledge this limitation and discuss its implications (Discussion section, approx. lines 283–302)
- Sample size and generalizability: The relatively small sample size (n = 38) and single-center design limit the generalizability of the findings. Although this is acknowledged in the limitations section, a more critical discussion of how these factors may have influenced the results would strengthen the manuscript (Limitations section, approx. lines 399–408)
- Potential confounding factors: The observed underfeeding may be influenced by ICU-specific feeding protocols (e.g., gradual feeding progression in the first days of admission). This represents an important potential confounder that should be discussed in more depth, as it may partially explain the discrepancy between estimated and delivered energy (Discussion section, approx. lines 344–352).
Author Response
Dear Editor and Reviewers,
We would like to sincerely thank the Editor and the Reviewers for their careful evaluation of our manuscript and for their constructive comments and suggestions. We appreciate the opportunity to revise our manuscript and believe that the revisions have significantly improved the clarity and quality of the paper. All comments have been carefully considered, and the manuscript has been revised accordingly. Changes made in the manuscript are indicated in red. Below, we provide a detailed, point-by-point response to each comment.
Response to Reviewer #1:
Comments 1: The manuscript refers to the study as both “prospective” and “cross-sectional observational,” creating methodological ambiguity. The study design should be clearly and consistently defined throughout the manuscript. In addition, some redundancy should be avoided (e.g., repeated reporting of the sample size). Please revise for clarity and consistency (lines 125–134)
Response 1
We acknowledge that the use of both “prospective” and “cross-sectional observational” terms in the previous version of the manuscript created methodological ambiguity. In our study, indirect calorimetry measurements and all relevant clinical and questionnaire data were collected on the same day. In addition, patients’ in-hospital energy intake was recorded over a 3-day period. However, there was no longitudinal follow-up or repeated prospective assessment of participants over time. Therefore, the study does not meet the criteria for a prospective design. Accordingly, the manuscript has been revised, and the term “prospective” has been removed throughout. The study is now consistently defined as a cross-sectional observational study, and the relevant sections (Lines 134–138) have been updated to ensure clarity and consistency. In addition, repeated reporting of the sample size has been reviewed and unnecessary redundancies have been removed.
Comments 2: Although the study provides useful insights into discrepancies between estimated and delivered energy, it does not include relevant clinical outcomes (e.g., mortality, length of stay, complications). This limits the clinical applicability of the findings. The authors are encouraged to more explicitly acknowledge this limitation and discuss its implications (Discussion section, approx. lines 283–302)
Response 2:
The absence of clinical outcome measures, such as mortality, length of hospital stay, and complications, limits the clinical interpretability of our findings. Accordingly, the Discussion section has been revised to more explicitly emphasize this limitation. Although significant discrepancies were observed between estimated energy requirements, indirect calorimetry measurements, and delivered energy, the lack of clinical outcome data precludes the evaluation of the clinical impact of these differences within the scope of the present study. Furthermore, the Discussion has been expanded to address the potential implications of these findings. Such discrepancies may contribute to risks of underfeeding or overfeeding in critically ill patients; however, this relationship remains speculative and cannot be confirmed based on our data. In addition, relevant and up-to-date references have been incorporated into the Discussion to better support this aspect (Lines 336–344, Page 8-9). In addition, these clinical factors may partly explain the discrepancy between estimated energy requirements and delivered energy intake observed in routine ICU practice
Comments 3: The relatively small sample size (n = 38) and single-center design limit the generalizability of the findings. Although this is acknowledged in the limitations section, a more critical discussion of how these factors may have influenced the results would strengthen the manuscript (Limitations section, approx. lines 399–408).
Response 3: We sincerely thank the reviewer for this important comment. We agree that the relatively small sample size (n = 38) and the single-center design may limit the external validity and generalizability of our findings. Although all eligible patients from the intensive care units within our hospital who met the inclusion criteria were enrolled during the study period, the strict inclusion criteria and the observational study design resulted in a limited sample size. This may have reduced statistical power and limited the ability to fully capture the clinical and metabolic heterogeneity of critically ill patients, potentially affecting the robustness of subgroup interpretations. In addition, the single-center design may reflect local clinical practices and patient characteristics, which may limit the generalizability of the findings to other institutions and healthcare settings. Accordingly, the Limitations section has been updated and revised in greater detail (Line 447-455,Page11).
Comments 4: The observed underfeeding may be influenced by ICU-specific feeding protocols (e.g., gradual feeding progression in the first days of admission). This represents an important potential confounder that should be discussed in more depth, as it may partially explain the discrepancy between estimated and delivered energy (Discussion section, approx. lines 344–352)..
Response 4: We sincerely thank the reviewer for this valuable comment. In our study, actual energy intake was calculated as the mean of three consecutive days, including the measurement day. The patients included in this period were those who tolerated feeding, and in whom nutritional intake had been gradually advanced toward target levels. Therefore, the analysis mainly reflects patients who were able to tolerate enteral or parenteral nutrition and achieve a more stable energy intake, rather than those in the very early phase of low-dose feeding.
Although ICU nutritional protocols often involve gradual advancement of feeding, using a three-day average helps to reduce the impact of daily fluctuations in energy delivery. However, inter-patient differences in feeding tolerance and variability in the rate of advancement toward target nutrition may still influence the mean energy intake. This should be taken into consideration when interpreting the discrepancy between estimated energy requirements and delivered energy (Line 386-394,Page 10). This approach was intended to better reflect routine clinical nutritional practice in the ICU.
Reviewer 2 Report
Comments and Suggestions for Authors
The authors have provided a nicely detailed and thorough response to the comments from the previous review and have addressed my major concerns. However, some comments need additional details:
- The Introduction should clearly and explicitly define the research gap, including what is missing from the literature, why existing studies are insufficient, and how this study addresses that gap in a concise and visible manner.
- The study objective should be stated once, clearly and concisely, and positioned at the end of the Introduction. Redundant or repeated formulations throughout the manuscript should be removed.
- The authors should explicitly address the conceptual limitation of comparing estimated energy needs with actual intake, clarifying how clinical factors influence intake and how this impacts the interpretation of results beyond simple rewording.
- The definition should be briefly introduced in the Introduction and used consistently throughout the manuscript, with clarification on whether it reflects delivered or absorbed intake and acknowledgment of its limitations.
- The manuscript should provide a balanced discussion of indirect calorimetry, including its limitations (cost, feasibility, accessibility), and avoid presenting it uncritically as the gold standard.
- The manuscript should specify how confounding factors and variability in clinical practice are considered in the analysis and how they influence the interpretation of findings.
- The conclusion should be concise, avoid repetition, and include clear and practical implications for clinical practice rather than remaining purely descriptive.
Author Response
Dear Reviewer,
We sincerely thank Reviewer 2 for carefully reviewing our manuscript and for the constructive feedback. We are pleased that our responses in the previous revision have addressed the main concerns and contributed to improving the manuscript. We also thank the reviewer for the comments and suggestions provided under the “Comments and Suggestions” section. All indicated revisions have been made, and the changes have been highlighted in red within the manuscript.
Response to Reviewer #2:
Comments 1: The Introduction should clearly and explicitly define the research gap, including what is missing from the literature, why existing studies are insufficient, and how this study addresses that gap in a concise and visible manner.
Response 1:
In response, we have revised the Introduction section to more clearly and explicitly define the research gap. Specifically, we clarified that the main gap in the literature is the lack of studies simultaneously comparing indirect calorimetry-derived energy requirements, commonly used predictive equations, and actual energy intake delivered in routine clinical ICU practice within the same patient population. We further emphasized that most existing studies focus either on estimated energy expenditure or on prescribed nutritional targets, without adequately reflecting real-world energy delivery at the bedside.
In the revised manuscript, we also highlighted that our study addresses this gap by directly comparing indirect calorimetry measurements, predictive equations (Harris–Benedict and ESPEN), and actual energy intake in critically ill ICU patients. This provides a more comprehensive assessment of how closely estimation methods reflect clinical practice and allows a clearer identification of discrepancies between calculated energy requirements and delivered energy in real-world ICU nutrition care. (Line 117-127,Page 3).
Comments 2: The study objective should be stated once, clearly and concisely, and positioned at the end of the Introduction. Redundant or repeated formulations throughout the manuscript should be removed.
Response 2:
In response, we have carefully revised the manuscript to ensure that the study objective is stated only once, clearly and concisely, and positioned at the end of the Introduction as recommended. Repeated statements of the study aim in the Introduction have been removed to eliminate redundancy and improve clarity.
In addition, we have also revised the Discussion section by removing repetitive expressions related to the study aim and scope. These statements were either deleted or consolidated to ensure a more concise, focused, and coherent presentation of the findings and interpretation.
Comments 3: The authors should explicitly address the conceptual limitation of comparing estimated energy needs with actual intake, clarifying how clinical factors influence intake and how this impacts the interpretation of results beyond simple rewording.
Response 3: We sincerely thank the reviewer for this valuable comment. In line with your suggestion, we have explicitly addressed the conceptual limitation of comparing estimated energy requirements with actual energy intake. Accordingly, a statement has been added to the Discussion section clarifying that actual energy intake in critically ill patients is influenced by multiple clinical factors, including feeding interruptions, gastrointestinal intolerance, hemodynamic instability, and stepwise nutritional protocols, which limits its direct comparability with estimated energy requirements. This revision helps to better reflect the clinical context and improve the interpretation of the study findings (Line 393-398,Page 10).
Comments 4: The definition should be briefly introduced in the Introduction and used consistently throughout the manuscript, with clarification on whether it reflects delivered or absorbed intake and acknowledgment of its limitations.
Response 4:
In line with this suggestion, the definition of “energy intake” has been clarified in our manuscript. In this study, energy intake refers to the amount of energy actually delivered to patients via enteral or parenteral nutrition, and it is not used interchangeably with metabolically absorbed energy. This clarification has been added to the Methods section, and the term has been used consistently throughout the manuscript. Therefore, the term “delivered energy intake” has been used throughout the manuscript instead of “actual energy intake.” Energy intake has been defined as the amount of energy actually delivered to patients via enteral or parenteral nutrition and this definition has also been stated in the Methods section (Line 211-214).
Comments 5: The manuscript should provide a balanced discussion of indirect calorimetry, including its limitations (cost, feasibility, accessibility), and avoid presenting it uncritically as the gold standard.
Response 5:
The description of indirect calorimetry (IC) as the “gold standard” is not an original claim of the authors but reflects its recognition as the reference method in current literature and clinical guidelines.
We would like to clarify that our intention was to accurately reflect the existing literature rather than to introduce or reinforce a biased interpretation. During the previous revision, we carefully reviewed and revised all statements that could potentially lead to misinterpretation or overstatement, with particular attention to avoiding bias. In the current revision, we have maintained the same level of rigor. Although IC is described as the reference or “gold standard” method in clinical guidelines, we have explicitly acknowledged its important practical limitations, including cost, limited availability, need for technical expertise, and challenges in routine clinical implementation. Therefore, weight-based predictive equations remain widely used in many clinical settings. In our study, these limitations were taken into consideration, and the practical applicability of IC was addressed in both the Discussion and Limitations sections (Lines 354–364, Page 9). Accordingly, the manuscript presents a balanced perspective that reflects both the established role of IC in the literature and its real-world constraints. We also included the ESPEN guideline (Singer et al., 2023), in which IC is described as the reference method, along with two additional supporting studies (Chandrasekaran et al., 2024; Kanshaov et al., 2025). Importantly, these sources also emphasize the limitations of IC in terms of cost, feasibility, and accessibility, which have been clearly acknowledged in our manuscript.
Chandrasekaran, A., Pal, D., Harne, R., Patel, S. J., Jagadeesh, K. N., Pachisia, A. V., Tyagi, P., Brar, K., Pattajoshi, S., Patel, P. B., Zatakiya, R., & Govil, D. (2024). Comparison between Effect of Indirect Calorimetry vs Weight-based Equation (25 kcal/kg/day)-guided Nutrition on Quadriceps Muscle Thickness as Assessed by Bedside Ultrasonography in Medical Intensive Care Unit Patients: A Randomized Clinical Trial. Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine, 28(6), 587–594. https://doi.org/10.5005/jp-journals-10071-24737; 1;
Kanshaov, N. Z., Leyderman, I. N., & Marichev, A. O. (2025). Actual energy expenditure in patients on extracorporeal membrane oxygenation: A modified indirect calorimetry vs. traditional approaches. Russian Journal of Anesthesiology and Reanimatology, (4), 6–12). This guideline was included in the manuscript as it directly highlights the limitations related to cost, feasibility, and accessibility of indirect calorimetry.
Singer, P.; Blaser, A. R.; Berger, M. M.; Calder, P. C.; Casaer, M.; Hiesmayr, M.; Mayer, K.; Montejo-Gonzalez, J. C.; Pichard, C.; Preiser, J. C.; Szczeklik, W.; van Zanten, A. R. H.; Bischoff, S. C. ESPEN practical and partially re-vised guideline: Clinical nutrition in the intensive care unit. Clin. Nutr. 2023, 42, 1671–1689. https://doi.org/10.1016/j.clnu.2023.07.011.
Comments 6: The manuscript should specify how confounding factors and variability in clinical practice are considered in the analysis and how they influence the interpretation of findings.
Response 6:
Key clinical variables such as disease severity, sepsis status, ventilatory support, hemodynamic instability, and feeding tolerance were carefully assessed using detailed patient records and clinical evaluation. These factors were taken into account during data interpretation to minimize the impact of potential confounding and to better reflect real-world intensive care practice.
A single standardized nutritional protocol was applied across all intensive care units in the study. According to this protocol, enteral feeding was initiated at 10 mL/h and gradually increased in a stepwise manner over 24 hours based on patient tolerance. This standardized approach was used to minimize variability in clinical practice and to ensure consistency in nutritional management across all included patients. No major feeding interruptions requiring cessation of nutritional support were recorded. (Line 224-231,Page 6). Also, we have added a statement in the Limitations section acknowledging that, despite controlling for key confounding factors and applying a standardized feeding protocol, complete elimination of clinical variability is not feasible in critically ill patients, and that this may have influenced the interpretation of the findings (Line 466-475,Page 11-12).
Comments 7: The conclusion should be concise, avoid repetition, and include clear and practical implications for clinical practice rather than remaining purely descriptive.
Response 7:
The Conclusion section has been shortened, repetitive statements have been removed, and the text has been made more clinically focused. The revised version highlights the discrepancy between estimated, measured, and delivered energy in critically ill patients, as well as the tendency toward underfeeding in clinical practice. We also clarified that the routine use of indirect calorimetry is limited and emphasized the importance of careful monitoring of delivered energy when IC is not available (Lines 477–483, Page 12).
