Association Between ASA Physical Status Classification and Postoperative Intensive Care Requirement in Pediatric Patients Undergoing Dental Treatment Under General Anesthesia: A Retrospective Study
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsHello, dear colleagues!
This article addresses the important issue of preoperative risk stratification in children undergoing dental treatment under general anesthesia.
Despite the obvious merits of this work, which can be recommended for use in practical healthcare, I would like to draw attention to the following points, which require discussion and correction.
1. Limited medical record data, possible incompleteness or subjectivity in the records – this should be specified in the limitations of the Bechtsin methods.
2. Lack of analysis of the severity and control of systemic diseases: you only considered the presence of the disease, but not its degree of compensation, which could have influenced the risk and change in ASA class.
3. Limited observation time: only the need for intensive care in the first 24 hours was assessed; long-term outcomes were not studied.
The reference list contains individual references that are 10 or more years old. The introduction needs to be updated and revised.
Author Response
1Limited medical record data, possible incompleteness or subjectivity in the records – this should be specified in the limitations of the Bechtsin methods.
Response 1: We thank the reviewer for this valuable comment. In accordance with the suggestion, we have revised the Limitations section of the manuscript to explicitly address the retrospective reliance on medical records. We have now clarified the potential for incomplete or inconsistently documented clinical data, possible documentation bias, and the inherently subjective nature of ASA classification, including potential interobserver variability.
2.Lack of analysis of the severity and control of systemic diseases: you only considered the presence of the disease, but not its degree of compensation, which could have influenced the risk and change in ASA class.
Response 2: We thank the reviewer for this important observation. We agree that the severity and level of control (degree of compensation) of systemic diseases may significantly influence perioperative risk and ASA classification. Due to the retrospective design of the study and the structure of available medical records, systemic diseases were analyzed based on their documented presence rather than detailed information regarding severity, clinical staging, or level of control. We acknowledge that variations in disease compensation status could have affected both ASA categorization and postoperative intensive care risk. This limitation has now been explicitly addressed in the revised Limitations section of the manuscript.
3.Limited observation time: only the need for intensive care in the first 24 hours was assessed; long-term outcomes were not studied.
Response 3: We thank the reviewer for this important comment. We have revised the Limitations section to clearly state that postoperative outcomes were assessed only within the first 24 hours following general anesthesia.
4.The reference list contains individual references that are 10 or more years old. The introduction needs to be updated and revised.
Response 4: We thank the reviewer for this valuable suggestion. The Introduction section has been revised and updated accordingly. Older references were reviewed, and where appropriate, more recent and relevant literature has been incorporated to ensure the manuscript reflects the current state of knowledge. The reference list has been updated to improve the scientific relevance and timeliness of the study. The Introduction section has been revised and updated accordingly. Recent literature has been incorporated, and the background and rationale of the study have been further strengthened to better reflect current evidence and clearly define the research gap.
Reviewer 2 Report
Comments and Suggestions for AuthorsMethod
Explicitly state inclusion/exclusion criteria for ASA IV or higher patients.
Provide a clear operational definition of postoperative intensive care requirement, specifying ICU vs. PACU, clinical criteria, and monitoring thresholds.
the Discussion and Conclusion
Statements describing the ASA classification as a “comprehensive clinical indicator,” “predictive clinical parameter,” or a “resource management tool” represent overgeneralization given the single-center, retrospective nature of the study. Considerable repetition exists between the discussion and conclusion sections, with the conclusion largely restating earlier arguments rather than synthesizing key findings. Clinical and policy-level recommendations extend beyond what is directly supported by the data.
This manuscript investigates the association between ASA Physical Status Classification, systemic diseases, and postoperative intensive care unit (ICU) requirement in pediatric dental patients undergoing general anesthesia. The topic is clinically relevant, and the large sample size (n=1003) strengthens the study.
This study: Contributes directly to: Risk stratification before pediatric dental GA
ICU planning, The need for a multidisciplinary approach. It is particularly useful in practice from an anesthesiology perspective.
However, several major and minor revisions are required before the manuscript can be considered for publication.
MAJOR ISSUES
1. Study Design
The text mentions "retrospective and descriptive"; however, "Chi-square logistic regression was not used." Therefore, the study should be defined as "retrospective observational analytical study." The study should be described as a "retrospective observational analytical study" rather than descriptive.
2. ICU Admission Criteria
The need for postoperative ICU admission has been defined, but: Is it elective planned ICU admission? Is it due to unexpected complications? Is it influenced by institutional protocol? is not specified. Clarify whether ICU admissions were planned or unplanned and based on institutional protocol.
3. Logistic Regression Results
The text states that regression analysis was performed, however:OR, 95% CI, p-values are not presented in any table.Odds ratios, 95% confidence intervals, and p-values must be presented in a separate table.
4. Zero ICU Requirement in ASA I Group
This finding is striking, but: Selection bias? Were low-risk patients already discharged as outpatients? Was a short-term observation period used? These questions were not discussed. Possible selection bias and discharge protocols should be discussed.
5. Lack of Disease Severity Data
It was only evaluated as "yes/no". This is an important limitation.
It should be emphasized more strongly in the Limitations section. Severity and control status of systemic diseases were not analyzed and should be acknowledged as a limitation.
6. Age and ICU Relationship
The finding that older children required more ICU care should be clinically explained.
MINOR ISSUES
1.Shorten repetitive phrases : Some repetitions are present: “strong and significant association” “clinically meaningful tool”should be abbreviated.
2.Add regression findings to abstract
3.Standardize tables and reference formatting
CONCLUSION
Comments on the Quality of English Language
Some sentences are unnecessarily long and contain chained structures that reduce readability. The term “cost-advantageous” is not commonly used in academic writing and is terminologically debatable. The phrase “more positive behavior” is subjective and lacks clear measurability. The expression “have been shown to be longer lasting” is weak in terms of an unspecified subject and the level of supporting evidence.
The article contains numerous errors in English. A review would be appropriate
Author Response
1Method Explicitly state inclusion/exclusion criteria for ASA IV or higher patients. Provide a clear operational definition of postoperative intensive care requirement, specifying ICU vs. PACU, clinical criteria, and monitoring thresholds.
Response 1: We thank the reviewer for these valuable methodological comments. The inclusion and exclusion criteria have been revised to explicitly state that ASA IV or higher patients were excluded due to the small sample size and the distinct perioperative management protocols applied to this high-risk group. In addition, the operational definition of postoperative intensive care requirement has been expanded to clearly distinguish ICU admission from routine PACU monitoring and to specify the clinical criteria guiding ICU transfer. These clarifications have been incorporated into the Methods section.
2.The Discussion and Conclusion
Statements describing the ASA classification as a “comprehensive clinical indicator,” “predictive clinical parameter,” or a “resource management tool” represent overgeneralization given the single-center, retrospective nature of the study. Considerable repetition exists between the discussion and conclusion sections, with the conclusion largely restating earlier arguments rather than synthesizing key findings. Clinical and policy-level recommendations extend beyond what is directly supported by the data.
Response 2: We thank the reviewer for this valuable comment. We agree that some statements in the Discussion and Conclusion sections were overly strong given the retrospective, single-center design. The manuscript has been revised to moderate the language, remove overgeneralizations, and avoid policy-level implications. Redundant statements between the Discussion and Conclusion have also been reduced, and the Conclusion has been rewritten to provide a concise synthesis of the key findings without extending beyond the data.
3.This manuscript investigates the association between ASA Physical Status Classification, systemic diseases, and postoperative intensive care unit (ICU) requirement in pediatric dental patients undergoing general anesthesia. The topic is clinically relevant, and the large sample size (n=1003) strengthens the study. This study: Contributes directly to: Risk stratification before pediatric dental GA ICU planning, The need for a multidisciplinary approach. It is particularly useful in practice from an anesthesiology perspective. However, several major and minor revisions are required before the manuscript can be considered for publication.
Response 3: We sincerely thank the reviewer for the positive and constructive evaluation of our manuscript. We appreciate the recognition of the clinical relevance of the topic and the strength provided by the large sample size. We have carefully addressed all major and minor comments to improve the clarity, methodological rigor, and scientific balance of the manuscript.
MAJOR ISSUES
- Study Design
The text mentions "retrospective and descriptive"; however, "Chi-square logistic regression was not used." Therefore, the study should be defined as "retrospective observational analytical study." The study should be described as a "retrospective observational analytical study" rather than descriptive.
Response 1: We thank the reviewer for this valuable comment. We agree that, given the use of inferential statistical analyses including Chi-square testing and multivariate logistic regression, the study design is more accurately defined as a retrospective observational analytical study rather than purely descriptive. The Methods section has been revised accordingly.
2.ICU Admission Criteria
The need for postoperative ICU admission has been defined, but: Is it elective planned ICU admission? Is it due to unexpected complications? Is it influenced by institutional protocol? is not specified. Clarify whether ICU admissions were planned or unplanned and based on institutional protocol.
Response 2: We thank the reviewer for this important clarification request. The Methods section has been revised to clearly specify that ICU admissions were not routinely planned preoperatively but were determined postoperatively based on the patient’s clinical condition. ICU transfer decisions were made by the attending anesthesiologist according to immediate postoperative assessment and institutional practice, considering respiratory, hemodynamic, and neurological status.
3.Logistic Regression Results
The text states that regression analysis was performed, however: OR, 95% CI, p-values are not presented in any table. Odds ratios, 95% confidence intervals, and p-values must be presented in a separate table.
Response 3: ORs, 95% CIs, and p-values have now been presented in a separate table as requested. Additionally, an interaction term (ASA × age) was included in the multivariable model; no significant interaction effect was observed.
4.Zero ICU Requirement in ASA I Group
This finding is striking, but: Selection bias? Were low-risk patients already discharged as outpatients? Was a short-term observation period used? These questions were not discussed. Possible selection bias and discharge protocols should be discussed.
Response 4: We thank the reviewer for this important comment. We agree that the absence of ICU admission in the ASA I group warrants careful interpretation. The Discussion section has been revised to address potential influences.
5.Lack of Disease Severity Data;It was only evaluated as "yes/no". This is an important limitation. It should be emphasized more strongly in the Limitations section. Severity and control status of systemic diseases were not analyzed and should be acknowledged as a limitation.
Response 5: We thank the reviewer for highlighting this important point. We agree that the absence of detailed severity and control status data for systemic diseases represents a significant limitation. The Limitations section has been revised to more explicitly acknowledge that systemic conditions were recorded as present/absent without standardized grading of severity or control status, which may have influenced risk interpretation.
6.Age and ICU Relationship
The finding that older children required more ICU care should be clinically explained.
Response 6: We thank the reviewer for this important suggestion. The Discussion section has been expanded to provide a clinical explanation for the observed association between older age and increased ICU requirement, considering disease complexity and potential procedural factors.
MINOR ISSUES
1.Shorten repetitive phrases: Some repetitions are present: “strong and significant association” “clinically meaningful tool”should be abbreviated.
Response 1: We thank the reviewer for this helpful comment. The manuscript has been revised to remove redundant phrasing and to moderate the language.
2.Add regression findings to abstract
Response 2: Thank you for this suggestion. The results of the multivariable logistic regression analysis have now been added to the Abstract. The Abstract has been revised accordingly.
3.Standardize tables and reference formatting
Response 3: We thank the reviewer for this helpful suggestion. The tables and reference formatting have been carefully reviewed and standardized according to the journal’s guidelines to ensure consistency and clarity throughout the manuscript.
CONCLUSION
1.The manuscript is valuable and publishable after minor revision.
Response 1: We sincerely thank the reviewer for the positive evaluation of our manuscript. We appreciate the constructive feedback and have carefully addressed all suggested revisions to further improve the clarity and quality of the study.
Comments on the Quality of English Language
1.Some sentences are unnecessarily long and contain chained structures that reduce readability. The term “cost-advantageous” is not commonly used in academic writing and is terminologically debatable. The phrase “more positive behavior” is subjective and lacks clear measurability. The expression “have been shown to be longer lasting” is weak in terms of an unspecified subject and the level of supporting evidence. The article contains numerous errors in English. A review would be appropriate
Response 1: We thank the reviewer for these valuable comments regarding language clarity and terminology. The manuscript has been carefully revised to improve readability and eliminate unnecessarily long or chained sentence structures. e. The entire manuscript has undergone thorough English language editing to improve grammatical accuracy and academic tone.
Reviewer 3 Report
Comments and Suggestions for AuthorsThe study has clinical relevance and a strong sample size, but requires conceptual reframing, statistical correction, and toned-down conclusions to meet publication standards.
1. A fundamental conceptual flaw is that ASA classification already incorporates systemic disease burden by definition. Therefore, demonstrating an association between ASA class and systemic disease prevalence is tautological, not a novel finding. The manuscript repeatedly treats ASA as an independent predictor of systemic disease, when in reality systemic disease determines ASA, not vice versa.
2. “Postoperative intensive care requirement” is defined broadly (monitoring, respiratory support, hemodynamic follow-up), but no institutional criteria, protocol, or objective thresholds for ICU admission are described. ICU admission decisions are operator- and institution-dependent, introducing strong selection bias.
3. The paper implicitly argues that ASA classification can “predict postoperative care level.” However, ASA is not designed to predict ICU admission.
It is a preoperative descriptive tool, not a validated prognostic score.
4. The regression model includes ASA classification and presence of systemic disease. These variables are highly collinear, because systemic disease is embedded in ASA scoring. Odds ratios from this model are statistically unstable and uninterpretable. Remove “presence of systemic disease” from the regression.
5. Age is significantly higher in ICU patients (Table 3), but age is not stratified by ASA class. No interaction analysis (ASA × age) is presented.
6. Phrases such as “ASA classification is a predictive clinical parameter” and “ASA determines postoperative care level” are causal in tone, but the study is retrospective and observational.
7. The manuscript claims novelty by “directly and quantitatively demonstrating” ASA–ICU relationships. However, similar associations have already been shown in anesthesia and pediatric surgery literature. No new scoring system, threshold, or predictive model is introduced.
8. Tables 4 and 5 partially duplicate information already implicit in ASA definitions.
9. Ethics approval date (01.12.2025) appears after the study period (2022–2025).
Author Response
Reviewer 3:
The study has clinical relevance and a strong sample size, but requires conceptual reframing, statistical correction, and toned-down conclusions to meet publication standards.
- A fundamental conceptual flaw is that ASA classification already incorporates systemic disease burden by definition. Therefore, demonstrating an association between ASA class and systemic disease prevalence is tautological, not a novel finding. The manuscript repeatedly treats ASA as an independent predictor of systemic disease, when in reality systemic disease determines ASA, not vice versa.
Response 1: We thank the reviewer for this important conceptual observation. We agree that systemic disease burden is inherently embedded within the ASA classification framework, and therefore the association between ASA class and systemic disease prevalence is structurally expected rather than an independent analytical finding. To address this concern, we have revised the manuscript to clarify that the primary objective of the study is the association between ASA classification and postoperative intensive care unit admission, rather than the relationship between ASA and systemic disease itself. The discussion has been reframed accordingly to avoid conceptual redundancy.
- “Postoperative intensive care requirement” is defined broadly (monitoring, respiratory support, hemodynamic follow-up), but no institutional criteria, protocol, or objective thresholds for ICU admission are described. ICU admission decisions are operator- and institution-dependent, introducing strong selection bias.
Response 2: We appreciate the reviewer’s insightful comment. Postoperative ICU admission in our institution was not based on arbitrary or routine protocol-driven transfer but on predefined clinical indications documented in the medical records, including ventilatory support requirement, persistent oxygen desaturation (SpOâ‚‚ < 92% despite supplemental oxygen), hemodynamic instability requiring vasoactive support, and significant neurological impairment requiring close monitoring. These objective criteria have now been more clearly detailed in the Methods section. While these objective criteria were consistently applied within our institution, we acknowledge that decision-making may vary across centers, and therefore the findings should be interpreted within the context of institutional practice.
- The paper implicitly argues that ASA classification can “predict postoperative care level.” However, ASA is not designed to predict ICU admission. It is a preoperative descriptive tool, not a validated prognostic score.
Response 3: We thank the reviewer for this important clarification. We agree that the ASA Physical Status Classification was originally designed as a descriptive preoperative assessment tool rather than a validated prognostic score for predicting postoperative intensive care admission. Our intention was not to present ASA classification as a standalone predictive instrument, but rather to examine its association with postoperative intensive care requirement within a pediatric dental anesthesia setting. To address this concern, we have revised the manuscript to avoid language suggesting predictive validity and instead emphasize that ASA classification was analyzed as a preoperative summary indicator of systemic health status that showed a significant association with postoperative intensive care unit admission in this cohort.
- The regression model includes ASA classification and presence of systemic disease. These variables are highly collinear, because systemic disease is embedded in ASA scoring. Odds ratios from this model are statistically unstable and uninterpretable. Remove “presence of systemic disease” from the regression.
Response 4: Thank you for this important methodological observation. The variable “presence of systemic disease” has been removed from the multivariable logistic regression model.
- Age is significantly higher in ICU patients (Table 3), but age is not stratified by ASA class. No interaction analysis (ASA × age) is presented.
Response 5: Thank you for this valuable comment. In the revised manuscript, we performed an additional multivariable logistic regression analysis including an interaction term (ASA × age) to evaluate whether the association between ASA physical status and postoperative ICU requirement was modified by age.
- Phrases such as “ASA classification is a predictive clinical parameter” and “ASA determines postoperative care level” are causal in tone, but the study is retrospective and observational.
Response 6: We thank the reviewer for this important methodological comment. We have revised the manuscript to avoid causal expressions such as “determines” and “predictive parameter” and replaced them with association-based terminology.
- The manuscript claims novelty by “directly and quantitatively demonstrating” ASA–ICU relationships. However, similar associations have already been shown in anesthesia and pediatric surgery literature. No new scoring system, threshold, or predictive model is introduced.
Response 7: We thank the reviewer for this important observation. We agree that associations between ASA classification and postoperative outcomes have previously been reported in anesthesia and pediatric surgery literature. Our intention was not to claim novelty in the ASA–ICU relationship per se, but rather to highlight its evaluation within a pediatric dental general anesthesia population, which has been less extensively studied. Accordingly, we have revised the manuscript to moderate claims of novelty and to clarify that this study adds contextual evidence rather than introducing a new predictive model or scoring system.
- Tables 4 and 5 partially duplicate information already implicit in ASA definitions.
Response 8: We thank the reviewer for this insightful comment. Since systemic disease burden is conceptually embedded within the ASA classification system, we agree that presenting a detailed distribution of systemic diseases across ASA classes may lead to partial redundancy. Therefore, Table 5 has been removed, and the relationship has been briefly summarized in the Results section. The detailed systemic disease distribution table has been removed to avoid redundancy; the regression table remains.
- Ethics approval date (01.12.2025) appears after the study period (2022–2025).
Response 9: Thank you for this observation. The ethics approval date was initially written in day–month–year format (01.12.2025), which corresponds to 1 December 2025. To avoid confusion in the English-language format, the date has now been revised and clearly written as “12/01/2025” in the manuscript. For transparency and documentation purposes, a copy of the official ethics committee approval form has also been provided as a supplementary file.
Round 2
Reviewer 3 Report
Comments and Suggestions for AuthorsThe authors have substantially improved the manuscript and have appropriately addressed most of the conceptual and methodological concerns raised in the previous review. However, several issues remain that warrant clarification or additional refinement before the manuscript can be considered fully satisfactory.
1. Although the authors removed the collinear “presence of systemic disease” variable and added the ASA × age interaction term, a major statistical concern remains unresolved. Specifically, no ICU events occurred in the ASA I group. The multivariable model reports an odds ratio of 133.76 for ASA classification, with an extremely wide confidence interval (95% CI: 6.66–2686.57). This pattern strongly suggests quasi-complete separation and sparse data bias, which can substantially inflate point estimates and compromise model stability. While the authors acknowledge the wide confidence interval and sparse data structure in the Discussion, this does not resolve the underlying modeling issue. In situations with zero-event categories, conventional logistic regression may produce unstable or exaggerated odds ratios.
2. The Methods section now provides clearer clinical criteria for ICU admission, which improves transparency. However, ICU transfer decisions were still made by the attending anesthesiologist based on clinical judgment and institutional practice. Although objective parameters (SpOâ‚‚ threshold, ventilatory support, vasoactive requirement, neurological impairment) are listed, it remains unclear. The authors should clarify whether a standardized institutional ICU transfer protocol exists and explicitly acknowledge potential decision-making variability as a limitation affecting outcome classification.
3. The ethics approval date is listed as 12/01/2025, while the study period spans 2022–2025. Although retrospective approval is acceptable, clarification is needed regarding whether data collection was completed prior to ethical approval, or whether data extraction continued after approval was granted. The temporal relationship between study completion and ethics approval should be clearly stated to avoid ambiguity. Add one clarifying sentence in the Methods specifying that the study was retrospectively approved after completion of data collection (if applicable).
4. Although the prior systemic distribution table was removed, Table 4 still presents an extensive breakdown of systemic diseases across ICU status. Because systemic disease burden is inherently embedded within ASA classification, this detailed distribution may not contribute independently to the central research question (ASA–ICU association) and may partially duplicate conceptual information already acknowledged. Consider either condensing the systemic disease table to a summarized format, or moving the detailed breakdown to supplementary material.
Author Response
The authors have substantially improved the manuscript and have appropriately addressed most of the conceptual and methodological concerns raised in the previous review. However, several issues remain that warrant clarification or additional refinement before the manuscript can be considered fully satisfactory. We sincerely thank the reviewer for the careful re-evaluation of our manuscript and for acknowledging the improvements made in response to the previous comments. We have carefully addressed the remaining issues raised and have implemented additional clarifications and refinements in the revised version of the manuscript. All modifications have been clearly highlighted, and detailed point-by-point responses are provided below.
1. Although the authors removed the collinear “presence of systemic disease” variable and added the ASA × age interaction term, a major statistical concern remains unresolved. Specifically, no ICU events occurred in the ASA I group. The multivariable model reports an odds ratio of 133.76 for ASA classification, with an extremely wide confidence interval (95% CI: 6.66–2686.57). This pattern strongly suggests quasi-complete separation and sparse data bias, which can substantially inflate point estimates and compromise model stability. While the authors acknowledge the wide confidence interval and sparse data structure in the Discussion, this does not resolve the underlying modeling issue. In situations with zero-event categories, conventional logistic regression may produce unstable or exaggerated odds ratios. Response 1. We sincerely thank the reviewer for this important statistical concern regarding quasi-complete separation and sparse data bias. We agree that the absence of ICU events in the ASA I group may lead to instability and inflated effect estimates when conventional logistic regression is applied. In response to this concern, we have replaced the standard multivariable logistic regression analysis with a penalized likelihood logistic regression using Firth’s correction, which is specifically recommended for situations involving sparse data and zero-event categories. The Firth penalized regression analysis was conducted using the logistf package in R, and the revised results are now presented in Table 5. This approach provides bias-reduced and more stable parameter estimates. The association between ASA classification and postoperative ICU requirement remained statistically significant under the penalized model. We have updated the Methods section to clearly describe the use of Firth’s logistic regression and revised the Discussion section to reflect the implications of sparse data structure and the interpretation of effect magnitude.
2.The Methods section now provides clearer clinical criteria for ICU admission, which improves transparency. However, ICU transfer decisions were still made by the attending anesthesiologist based on clinical judgment and institutional practice. Although objective parameters (SpOâ‚‚ threshold, ventilatory support, vasoactive requirement, neurological impairment) are listed, it remains unclear. The authors should clarify whether a standardized institutional ICU transfer protocol exists and explicitly acknowledge potential decision-making variability as a limitation affecting outcome classification. Response 2. We thank the reviewer for this important comment regarding ICU transfer criteria and potential variability in decision-making. In our institution, postoperative recovery is initially assessed using the Modified Aldrete Score in combination with predefined clinical parameters, including oxygen saturation thresholds (SpOâ‚‚ < 92% despite supplemental oxygen), need for invasive or non-invasive ventilatory support, requirement for vasoactive agents, hemodynamic instability, and significant neurological impairment. These criteria constitute the structured institutional framework guiding ICU transfer decisions. Although objective parameters are consistently applied, final ICU transfer decisions are made by the attending anesthesiologist based on comprehensive postoperative clinical assessment. To address the reviewer’s concern, we have clarified in the Methods section that ICU admission decisions were guided by institutional criteria combined with anesthesiologist evaluation. Furthermore, we have explicitly acknowledged potential decision-making variability as a limitation in the Discussion section, noting that this may have influenced postoperative outcome classification.
3.The ethics approval date is listed as 12/01/2025, while the study period spans 2022–2025. Although retrospective approval is acceptable, clarification is needed regarding whether data collection was completed prior to ethical approval, or whether data extraction continued after approval was granted. The temporal relationship between study completion and ethics approval should be clearly stated to avoid ambiguity. Add one clarifying sentence in the Methods specifying that the study was retrospectively approved after completion of data collection (if applicable). Response 3. We thank the reviewer for highlighting this important issue regarding the temporal relationship between the study period and ethical approval. This study was conducted using retrospectively recorded clinical data that had been routinely collected between 2022 and 2025 as part of standard patient care. Ethical approval (Decision No: HRU/25.19.63; Date: 12/01/2025) was obtained retrospectively for the use of these existing records. No additional data were collected after ethical approval was granted, and data extraction and analysis were performed only after approval had been obtained. To clarify this temporal sequence and avoid ambiguity, we have added a sentence in the Methods section explicitly stating that the study was retrospectively approved after completion of data collection.
4.Although the prior systemic distribution table was removed, Table 4 still presents an extensive breakdown of systemic diseases across ICU status. Because systemic disease burden is inherently embedded within ASA classification, this detailed distribution may not contribute independently to the central research question (ASA–ICU association) and may partially duplicate conceptual information already acknowledged. Consider either condensing the systemic disease table to a summarized format, or moving the detailed breakdown to supplementary material. Response 4. We thank the reviewer for this valuable comment. We agree that ASA classification inherently reflects the systemic disease burden and represents the primary independent variable in this study. The detailed breakdown of individual systemic diseases was initially included to provide clinical transparency regarding the comorbidity profile of the cohort. However, we acknowledge that this level of detail may partially duplicate conceptual information and may not directly contribute to the ASA–ICU association. Accordingly, we have revised Table 4 by retaining the ASA classification analysis in the main manuscript and moving the detailed systemic disease distribution to the Supplementary Material.
Author Response File: 
Author Response.docx
