Trends and Challenges in Noninvasive Hemodynamic Monitoring of Neonates Following Cardiac Surgery: A Narrative Review

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This review covers an important area in neonatal cardiac critical care and does a good job summarizing the available monitoring tools. I think the manuscript could be strengthened by a few clarifications.

1. Much of the evidence for these monitoring modalities comes from small, single-center studies. It would help to point out where data are preliminary and where larger studies or multicenter validation are still needed.

2. For NIRS, the limitations need more emphasis. Signal contamination, device variability, and the lack of validated thresholds for intervention are major issues that affect clinical interpretation.

3. For electrical biosensing technologies, the correlations with echocardiography are useful, but accuracy is variable in neonates, especially in the setting of shunts or arrhythmias. This deserves more critical discussion.

4. The section on microcirculatory monitoring is interesting, but these technologies are still largely experimental, and the absence of neonatal reference values should be made clearer.

5. Since you conclude that multimodal monitoring is the future, it would be helpful to expand on how different modalities could be integrated in practice and how they complement each other in guiding management.

Author Response

Thank you very much for taking the time to review this manuscript. Please find the detailed responses below and the corresponding revisions in track changes in the re-submitted files.

Comments 1: Much of the evidence for these monitoring modalities comes from small, single-center studies. It would help to point out where data are preliminary and where larger studies or multicenter validation are still needed.

Response 1: Thank you for pointing this out. We agree. Therefore, we pointed out this information, especially regarding studies involving electrical biosensing technology and microcirculatory monitoring.

Comments 2: For NIRS, the limitations need more emphasis. Signal contamination, device variability, and the lack of validated thresholds for intervention are major issues that affect clinical interpretation.

Response 2: We added a paragraph listing the major limitations of NIRS monitoring, as well as further emphasizing the lack of validated threshold for intervention. Moreover, we included two studies showing the impact on mortality and neurodevelopmental outcomes.

Comments 3: For electrical biosensing technologies, the correlations with echocardiography are useful, but accuracy is variable in neonates, especially in the setting of shunts or arrhythmias. This deserves more critical discussion.

Response 3: We agree. We also added a paragraph discussing EBT limitations.

Comments 4: The section on microcirculatory monitoring is interesting, but these technologies are still largely experimental, and the absence of neonatal reference values should be made clearer.

Response 4: We mentioned that a major limitation of microcirculatory monitoring remains the absence of standardized reference values in neonates and infants. We further emphasized that the use of HVM devices is still largely experimental and microcirculatory monitoring has yet to be incorporated into standard clinical care.

Comments 5: Since you conclude that multimodal monitoring is the future, it would be helpful to expand on how different modalities could be integrated in practice and how they complement each other in guiding management.

Response 5: We provide the example of our unit where such a multimodular monitoring platform is currently operational. We further added a paragraph discussing how different data from different devices complement each other and help in facilitating personalized management.

Author Response File: Author Response.docx

Reviewer 2 Report

Comments and Suggestions for Authors

Please refer to the attachment

Comments for author File: Comments.pdf

Author Response

Thank you very much for taking the time to review this manuscript. Please find the detailed responses below and the corresponding revisions in track changes in the re-submitted files.

Comments 1: Methodology Lacks Transparency and Systematic Rigor. While the authors mention a systematic search of PubMed, et al., the methodology section is underdeveloped. There is no PRISMA-style flow diagram, detailed inclusion/exclusion criteria, or a critical assessment of the quality and risk of bias of the included studies.

Response 1: Thank you for pointing this out. We did not develop a PRISMA-style flow diagram because we considered it more suitable for a systematic review. However, we provided more details on the database search in the Appendix. We included articles resulting from searching PubMed and Embase databases using the terms: “neonate” OR “newborn” OR “infant” AND “congenital heart disease” OR “heart disease” OR “CHD” AND “cardiac surgery” OR “cardiac procedure” OR “cardiac intervention” AND “hemodynamic” OR “hemodynamics”, as well as relevant articles found by manual search. We excluded articles from more than 10 years ago, articles with full texts in other language than English, as well as articles that did not align with the review's conceptual scope.

Comments 2: Insufficient Critical Appraisal of the Literature. The review predominantly describes and lists findings from other studies without providing a critical synthesis. The strengths and weaknesses of the cited evidence, sample size limitations, and consistency of findings across studies are not adequately discussed.

Response 2: Thank you for pointing this out. We agree. Therefore, we pointed out that most of the studies investigating, especially electrical biosensing technology and microcirculatory monitoring, were small and single-center. This limits statistical power and reduces the generalizability of the findings. Larger, multicenter studies are needed to validate these results.

Comments 3: Superficial Analysis of Certain Technologies. The description of several key technologies (e.g., NIRS, Electrical Biosensing Technology) remains superficial. The review misses opportunities to delve deeper into their comparative accuracy, population-specific applicability (e.g., single-ventricle vs. biventricular physiology), and most importantly, their impact on hard clinical outcomes (e.g., mortality, length of stay, neurodevelopmental outcomes).

Response 3: We agree. We added a paragraph listing the major limitations of NIRS monitoring, as well as further emphasizing the lack of validated threshold for intervention. Moreover, we included two studies showing the impact of NIRS monitoring in the perioperative period on mortality and neurodevelopmental outcomes.

Comments 4: Tables and Figures Require Improvement. Table 1 is poorly forma ed, making the formulas for VIS, VI, and VVR difficult to read and interpret. Source or create schematic figures that explain concepts (e.g., how EBT works) rather than relying solely on center-specific patient monitor images.

Response 4: We included a figure explaining how electrical biosensing technology works.

Comments 5: Future Directions Section is Vague. The section on future directions is generic and does not engage with cutting-edge developments. The mention of a multi-modal "tower" is noted, but the discussion lacks depth on how data integration, predictive algorithms, machine learning, or artificial intelligence could transform hemodynamic monitoring and personalized treatment.

Response 5: We further added a paragraph discussing how different data from different devices complement each other and help in facilitating personalized management.

Comments 6: Line 95-102 should be moved to introduction section.

Response 6: Thank you for the recommendation. We moved the paragraph to the introduction section.

Comments 7: There are typographical errors (e.g., "Lijc" on page 8), inconsistent citation formatting in the reference list, and repetitive figure legends. The language, while generally clear, would benefit from professional polishing to achieve a more concise and academic tone.

Response 7: Thank you for pointing this out. We corrected the typographical errors and the repetitive figure legends. We have sent the manuscript for review by an English language expert and have revised certain language mistakes.

Comments 8: The review enthusiastically promotes noninvasive techniques but does not sufficiently dedicate space to their inherent limitations in the neonatal population (e.g., susceptibility to motion artifact, calibration drift, the confounding effect of shunts, and limited validation in specific CHD subtypes).

Response 8: Thank you for your comment. We further emphasized these limitations.

Comments 9: Most of the references are too old, not recent 5 years.

Response 9: This is true because we used the last 10 years as the background for our literature review. To these, we added relevant studies that described the mechanisms of the monitoring devices or general principles in hemodynamic monitoring.

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

The authors have addressed most of my concerns. Two remains.

1. It might be more appropriate to move the first paragraph of the introduction to the final paragraph of the introduction.
2. It should highlight "Trends and Challenges in Noninvasive Hemodynamic Monitoring" in the title more prominently. Thus, it's not the problem that the references are too old (Comment 9); having and discussing most recent literatures could help solve the problem.

Author Response

Comment 1: It might be more appropriate to move the first paragraph of the introduction to the final paragraph of the introduction.

Response 1: We have adressed this issue.

Comment 2: It should highlight "Trends and Challenges in Noninvasive Hemodynamic Monitoring" in the title more prominently. Thus, it's not the problem that the references are too old (Comment 9); having and discussing most recent literatures could help solve the problem.

Response 2: Thank you very much for clarifying this. We added the most recent recommendations issued in 2020 by ESPNIC regarding hemodynamic monitoring in critically ill children. We focused on their conclusions regarding blood pressure and central venous pressure, echocardiography and NIRS. We already mentioned the recommendations issued by European Society for Pediatric Research in 2024 regarding electrical biosensing technology. We believe that after the first revision round we have emphasized the specific limitations of each hemodynamic monitoring method in this particular population - neonates with congenital heart disease, as well as some of the most relevant and recent clinical trials. Unfortunately the literature is still scarce regarding the use of microcirculatory monitoring devices or electrical biosensing technology in this population, and even more in this particular set-up (post-cardiac surgery), which is why their us remains mainly experimental and they are yet to be recommended for clinical practice. We have adjusted the Conclusion section in order to emphasize the  current trends (advances in technology, new noninvasive methods, changes in clinical practice), as well as challenges (validation issues, limitations in neonates, lack of standardization, technical barriers).