PONE-D-24-34309A scoping review protocol on brain PCO2 levels at altitudePLOS ONE

Dear Dr. Tang,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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Masaki Mogi

Academic Editor

PLOS ONE

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Additional Editor Comments:

The manuscript has been evaluated by two reviewers. See the suggestions carefully and respond them appropriately.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #1: Yes

Reviewer #2: Yes

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2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #1: Yes

Reviewer #2: Yes

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3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible.

Reviewer #1: Yes

Reviewer #2: Yes

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4. Have the authors described where all data underlying the findings will be made available when the study is complete?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Tang and colleagues described a scoping review protocol that maps the current literature to determine if blood arterial pressure of CO2 (PaCO2) acutely changes at high altitudes during aeromedical transportation. The authors provide details of how the study will be conducted, including inclusion and exclusion criteria, search strategy, evidence selection, data extraction and analysis. Overall, this protocol could be novel to understanding the PaCO2 changes in patients with ischemic stroke during aeromedical transportation.

Points of concern are outlined below:

1.Helicopter cabins are usually not pressurized. Since cabin pressure is not considered an inclusion criteria factor, the authors should include a short discussion on how cabin pressure may affect the PaCO2.

2.The authors mention in lines 173-175 that the current protocol may have a potential limitation in that the number of related studies may be small. Do the authors have an estimated number of literatures before and after the screening?

3.Please provide a discussion session that expands on the current “Strengths and Limitations” and briefly elaborates on factors like high altitude exposure format (helicopter, airliners, mountain climbing, chamber), exposure time, etc, that could complicate data interpretation.

4.Keep the PaCO2 acronym consistent.

Reviewer #2: Title: A scoping review protocol on brain PCO2 levels at altitude

Here is the review of the manuscript by Hanna Tang et al., which is a scoping review protocol on brain PCO₂ levels at altitude in critically ill patients. The authors address an interesting and clinically relevant question about the potential effects of rapid changes in altitude and atmospheric pressure on cerebral perfusion and ischemic burden during aeromedical transport of patients with ischemic stroke. This is a well-written and engaging scoping review protocol that clearly outlines the objectives, methods, and reporting approach for the review.

That said, I have a few minor suggestions for improvement:

Exclusion Criteria: The authors indicate that they will exclude studies involving participants under 18 years of age. However, it is unclear why this exclusion criterion is necessary for their review.

Measurement of PaCO₂: The authors specifically aim to include studies that report arterial partial pressure of CO₂ (PaCO₂) at two different altitudes. Since studies may measure PaCO₂ either directly (e.g., via arterial blood gas) or indirectly, the authors should clarify their criteria regarding acceptable methods for PaCO₂ measurement.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

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A scoping review protocol on brain PaCO2 levels at altitude

PONE-D-24-34309R1

Dear Dr. Tang,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Masaki Mogi

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #1: Yes

Reviewer #2: Yes

**********

2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible.

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors described where all data underlying the findings will be made available when the study is complete?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Tang and colleagues described a scoping review protocol that maps the current literature to determine if blood arterial pressure of CO2 (PaCO2) acutely changes at high altitudes during aeromedical transportation. The authors provide details of how the study will be conducted, including inclusion and exclusion criteria, search strategy, evidence selection, data extraction and analysis. Overall, this protocol could be novel to understanding the PaCO2 changes in patients with ischemic stroke during aeromedical transportation. The authors have addressed all my concerns. I don't have any further comments.

Reviewer #2: Here is the review of the manuscript by Hanna Tang et al., which is a scoping review protocol on brain PCO₂ levels at altitude in critically ill patients. The authors address an interesting and clinically relevant question about the potential effects of rapid changes in altitude and atmospheric pressure on cerebral perfusion and ischemic burden during aeromedical transport of patients with ischemic stroke. This is a well-written and engaging scoping review protocol that clearly outlines the objectives, methods, and reporting approach for the review. The concerns I had now well addressed and I suggest accepting the manuscript.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

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