Peer Review History

Original SubmissionJanuary 19, 2022
Decision Letter - Steven Eric Wolf, Editor

PONE-D-22-01880Optimal Duration of the Apnea Test for Determining Brain Death: Benefit of the Short-Term Apnea TestPLOS ONE

Dear Dr. Hong,

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.

Editor - Thank you for submitting your paper to us for review.  I sent it to three distinguished referees for comment and decision, and then three more of whom two agreed to review; you will see these below.  They thought that the paper has merit, but each have raised some issues to be addressed in a revision.  Please carefully consider the comments below and reply directly to each in a cover letter with appropriate marked and linked changes to the manuscript.  I look forward to seeing the revision, which I will handle personally for timeliness.  Please understand that this is not a guarantee of future publication, as the revised manuscript itself must stand on its own merit.

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Kind regards,

Steven Eric Wolf, MD

Academic Editor

PLOS ONE

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Reviewers' comments:

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Comments to the Author

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Reviewer #1: Yes

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Overall well written manuscript, addresses a clinically important issue for which a significant amount of controversy exists.

Only a few suggestions:

1. Clarify in the result section and Table #1, when describing most common causes of brain death "Traumatic hemorrhage" and "Non traumatic hemorrhage". Please clarify that these are intracranial hemorrhages or describe appropriately

2. Unclear if within 5 minutes all patients had a PaCO2 above 60 mmHg. If that is the case, state that all patients achieve this goal. If not, stare the percent that did.

Reviewer #2: A standard time interval for the apnea test has been suggested by national societies but not formalized by the international medical community. This paper is an attempt at starting that process, but because of varying ethical and legal standards, one paper will not complete the process. The scientific and statistical methods used by the authors are sound and are supported by the provided data. The choice of the smallest time interval that is satisfactory from a PaCO2 endpoint for protection of organs for transplantation is understandable but may be hard to achieve consensus. The additional time suggested by the American Academy of Neurology should not incur too great an oxygen debt or acidemia. As shown by this paper, the hemodynamics are usually easily controlled with vasoactive infusions. Some patients will in fact have intact brainstem reflexes that were not appreciated until the apnea test. Before the patient is declared dead, physicians still owe them a fiduciary duty. As suggested in this paper, future work should also focus on standardizing the balance of the protocol of the apnea test. The presented protocol is reasonable if the additional time is added.

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Reviewer #1: No

Reviewer #2: Yes: J. Sean Funston, M.D.

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Revision 1

Responses to reviewers’ comments

The authors would like to thank the reviewers for their constructive critique to improve the manuscript. We have made every effort to address the issues raised and to respond to all comments. The revisions are indicated in red font in the revised manuscript. Please, find next a detailed, point-by-point response to the reviewers’ comments. We hope that our revisions would meet the reviewers’ expectations.

Sincerely,

Kyung Sook Hong

E-mail: hongks@ewha.ac.kr

Reviewer #1

1. Clarify in the result section and Table #1, when describing most common causes of brain death "Traumatic hemorrhage" and "Non traumatic hemorrhage". Please clarify that these are intracranial hemorrhages or describe

Response: We would like to thank the reviewer for evaluating our manuscript and for the insightful comment. Please note that both “traumatic hemorrhage” and “non-traumatic hemorrhage” are intracranial hemorrhages. As per the reviewer’s suggestion, we have added the relevant information to Table 1.

2. Unclear if within 5 minutes all patients had a PaCO2 above 60 mmHg. If that is the case, state that all patients achieve this goal. If not, stare the percent that did.

Response: We would like to thank the reviewer for the kind comments to improve our manuscript. To convey accurate information to our readers, we have added relevant contents, as per the reviewer’s comments. Additionally, the positive criterion for apnea test in Korea is a PaCO2 level of ≥50 mmHg. Therefore, PaCO2 levels >60 mmHg were not observed in all patients. As per the reviewer’s suggestion, we have added the following sentence to the revised manuscript:

“In this study, the PaCO2 level exceeded 60 mmHg within 5 min in 76 (88.4%) and 81 (94.2%) cases of the 1st and 2nd apnea tests, respectively.”

Reviewer #2

1. A standard time interval for the apnea test has been suggested by national societies but not formalized by the international medical community. This paper is an attempt at starting that process, but because of varying ethical and legal standards, one paper will not complete the process. The scientific and statistical methods used by the authors are sound and are supported by the provided data. The choice of the smallest time interval that is satisfactory from a PaCO2 endpoint for protection of organs for transplantation is understandable but may be hard to achieve consensus. The additional time suggested by the American Academy of Neurology should not incur too great an oxygen debt or acidemia. As shown by this paper, the hemodynamics are usually easily controlled with vasoactive infusions. Some patients will in fact have intact brainstem reflexes that were not appreciated until the apnea test. Before the patient is declared dead, physicians still owe them a fiduciary duty. As suggested in this paper, future work should also focus on standardizing the balance of the protocol of the apnea test. The presented protocol is reasonable if the additional time is added.

Response: We would like to thank the reviewer for evaluating our manuscript and for his/her insightful comment. In the conclusion, we have stated that the appropriate duration of the apnea test is approximately 5 min. There are various debates concerning the duration of the apnea test for determination of brain death in Korea. As per the reviewer’s comments, we agree that the determination of brain death must be accompanied by ethical considerations. Therefore, as a further study, we will investigate the status of apnea tests in various institutions of Korea and plan ethical and reasonable suggestions for the positive criteria for apnea tests, including duration.

Attachments
Attachment
Submitted filename: Response to Editors and Reviewers.docx
Decision Letter - Steven Eric Wolf, Editor

Optimal Duration of the Apnea Test for Determining Brain Death: Benefit of the Short-Term Apnea Test

PONE-D-22-01880R1

Dear Dr. Hong,

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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Kind regards,

Steven Eric Wolf, MD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Formally Accepted
Acceptance Letter - Steven Eric Wolf, Editor

PONE-D-22-01880R1

Optimal Duration of the Apnea Test for Determining Brain Death: Benefit of the Short-Term Apnea Test

Dear Dr. Hong:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. 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.

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Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Steven Eric Wolf

Academic Editor

PLOS ONE

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