How effective is extracorporeal life support for patients with out-of-hospital cardiac arrest initiated at the emergency department? A systematic review and meta-analysis

Wachira Wongtanasarasin; Sarunsorn Krintratun; Witina Techasatian; Daniel K. Nishijima

doi:10.1371/journal.pone.0289054

Peer Review History

Original SubmissionMay 15, 2023
15 Jun 2023 Decision Letter - Gaetano Santulli, Editor PONE-D-23-14334How effective is extracorporeal life support for patients with out-of-hospital cardiac arrest initiated at the emergency department? A systematic review and meta-analysisPLOS ONE Dear Dr. Wongtanasarasin, 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 major concerns raised during the review process. Please submit your revised manuscript by Jul 30 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. 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The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf 2. We note that the grant information you provided in the ‘Funding Information’ and ‘Financial Disclosure’ sections do not match. When you resubmit, please ensure that you provide the correct grant numbers for the awards you received for your study in the ‘Funding Information’ section. 3. We note that you have referenced (unpublished) on page 5 which has currently not yet been accepted for publication. Please remove this from your References and amend this to state in the body of your manuscript: (ie “Bewick et al. [Unpublished]”) as detailed online in our guide for authors http://journals.plos.org/plosone/s/submission-guidelines#loc-reference-style. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: No Reviewer #2: Partly ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: No Reviewer #2: I Don't Know ****** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). 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: No Reviewer #2: Yes ****** 4. 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: No Reviewer #2: Yes ****** 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: The authors conducted a systematic review with meta-analysis with the aim of investigating the benefits of initiating ECPR in the emergency department for OHCA patients and concluded that ED-initiated ECPR may not be associated with increased favorable neurological outcomes but may be associated with improved survival to hospital discharge. The authors state that the aim is to investigate ECPR when initiated in the ED but they included a RCT where ECPR was initiated in the cath lab (Yannopoulos et al. Lancet 2020). I'm sorry but this is a major methodological issue that invalids all the analyses and conclusions presented. Moreover, to date there are 4 RCTs available and meta-analyses of randomized data only already indicated a benefit of this invervention. Reviewer #2: This is a systematic review and meta-analysis to evaluate the efficacy of ECPR for OHCA patients. This is hot topic, but there were several systematic review and meta-analysis for the efficacy of ECPR. I have several comments. Abstract P3 L47. “ECPR devices” Please clarify. It seems strange to mention this in conclusion. Method Please clarify the “ED”. Does it include both cardiac catheterization lab and emergency room? How about the operation room? Do the studies included in the meta-analysis contain the same patients? For example, reference 13 and 34 were the same country and duplicate periods. Conclusion Authors state that “In addition, it is important to invest in training emergency physicians on ECPR and ensure that the necessary equipment and facilities are available in the ED.” This is not based on results or discussions. ****** 6. 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 ******** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0289054.r001
Revision 1
24 Jun 2023 Author Response Response to Reviewers Reviewer #1: The authors conducted a systematic review with meta-analysis with the aim of investigating the benefits of initiating ECPR in the emergency department for OHCA patients and concluded that ED-initiated ECPR may not be associated with increased favorable neurological outcomes but may be associated with improved survival to hospital discharge. The authors state that the aim is to investigate ECPR when initiated in the ED but they included a RCT where ECPR was initiated in the cath lab (Yannopoulos et al. Lancet 2020). I'm sorry but this is a major methodological issue that invalids all the analyses and conclusions presented. Moreover, to date there are 4 RCTs available and meta-analyses of randomized data only already indicated a benefit of this invervention. Response: Reviewer #1 raises a concern regarding the inclusion of one study (Yannopoulos et al., Lancet 2020) in this systematic review and meta-analysis. The reviewer suggests that including this study, where ECPR was initiated in the cardiac cath lab rather than the ED, is a major methodological issue that invalidates the analyses and conclusions. We appreciate the reviewer's valuable input in identifying this error. We sincerely apologize for this oversight, as it does introduce bias and affects the validity of the conclusion. To address this issue, we revise our methodology and exclude a study by Yannopoulos et al. from our analysis. The results remain similar to the previous analyses. Since that study is a randomized controlled trial, the analyses of observational studies’ data were not changed (Figures 2a and 3a). In addition, the forest plots for propensity score (PPS) analysis after the exclusion of one study were similar to the previous plots (Figures 2b and 3b), as ED-initiated ECPR was associated with improved outcomes when only PPS data was analyzed. We recognize the importance of a rigorous review based on the intended inclusion criteria and focusing on studies that align with the specific setting of interest. The text changes regarding the exclusion of this study as well as the figures 1-4 were edited in the revised manuscript. Reviewer #2: This is a systematic review and meta-analysis to evaluate the efficacy of ECPR for OHCA patients. This is hot topic, but there were several systematic review and meta-analysis for the efficacy of ECPR. I have several comments. Abstract P3 L47. “ECPR devices” Please clarify. It seems strange to mention this in conclusion. Response: Thank you for your comment. The term “ECPR devices” refers to the various mechanical circulatory support systems and devices used to provide extracorporeal cardiopulmonary resuscitation (ECPR) in the context of cardiac arrest. We would like to say that included studies in this review applied the different types of ECPR devices, resulting in a heterogeneity of the combined data (i.e., there is no standard recommendation for using the ECPR devices during OHCA). We remove this term in the conclusion since it may result in some misunderstanding of the readers after careful discussion of all authors (Page 3 Line 46). Method Please clarify the “ED”. Does it include both cardiac catheterization lab and emergency room? How about the operation room? Response: We apologize for any confusion caused. We included only studies investigating the benefit of ECPR for OHCA patients at the emergency department. To clarify, the term “ED” in our study specifically refers to the “emergency department,” and it does not encompass the cardiac catheterization lab or the operating room. We focused on investigating the benefits of ECPR when initiated in the emergency department as it is the primary area where OHCA patients are initially transferred upon arrival at the hospital. Our aim was to assess the potential advantages of early initiation of ECPR in the ED setting. Do the studies included in the meta-analysis contain the same patients? For example, reference 13 and 34 were the same country and duplicate periods. Response: Thank you for providing additional clarification regarding references 13 and 34. In a meta-analysis, it is common to include studies conducted in the same country and overlapping periods (i.e., refs 13 and 34) as long as they provide distinct data and contribute to the overall understanding of the research question. During the data screening and extraction process, we carefully checked whether different included studies included the same population by two authors. We appreciate the clarification here and reviewed each included study again to ensure we include different patient populations in our meta-analysis. Conclusion Authors state that “In addition, it is important to invest in training emergency physicians on ECPR and ensure that the necessary equipment and facilities are available in the ED.” This is not based on results or discussions. Response: Thank you for pointing out the concern regarding this sentence that suggests the importance of investing in training emergency physicians on ECPR and ensuring the availability of necessary equipment and facilities in the ED. We acknowledge that this conclusion is not directly supported by the results or discussions presented in the manuscript. We apologize for any misinterpretation caused by the inclusion of this sentence. As a reviewer, you play a crucial role in ensuring the accuracy and relevance of the manuscript, and we appreciate your agreement with this concern. We remove this sentence in the revised manuscript (Page 15 Line 282). Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0289054.r002
6 Jul 2023 Decision Letter - Gaetano Santulli, Editor PONE-D-23-14334R1How effective is extracorporeal life support for patients with out-of-hospital cardiac arrest initiated at the emergency department? A systematic review and meta-analysisPLOS ONE Dear Dr. Wongtanasarasin, 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. Please submit your revised manuscript by Aug 20 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. Please include the following items when submitting your revised manuscript: A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'. An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols. We look forward to receiving your revised manuscript. Kind regards, Gaetano Santulli Academic Editor PLOS ONE Journal Requirements: Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice. Additional Editor Comments : English language (syntax, grammar, correct choice of words, correct use of adjectives and adverbs) needs significant editing throughout the text. Professional assistance must be sought. [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0289054.r003
Revision 2
9 Jul 2023 Author Response We would like to express our sincere gratitude for the opportunity to revise our manuscript. Changes are marked with tracked changes and an unmarked version of the revised paper without tracked changes is provided. Editor Comments : English language (syntax, grammar, correct choice of words, correct use of adjectives and adverbs) needs significant editing throughout the text. Professional assistance must be sought. Response: We sincerely appreciate the feedback provided. We have carefully considered your suggestions and taken necessary measures to significantly enhance the syntax, grammar, word choice, and appropriate usage of objectives and adverbs throughout the text. To ensure the utmost quality and professionalism in our writing, we engaged a specialized professional language editor. Their expertise allowed for meticulous revisions, greatly improving the document's readability and coherence. Changes are marked with tracked changes throughout the revised manuscript. Attachments Attachment Submitted filename: Response to Reviewers-R2.docx https://doi.org/10.1371/journal.pone.0289054.r004
11 Jul 2023 Decision Letter - Gaetano Santulli, Editor How effective is extracorporeal life support for patients with out-of-hospital cardiac arrest initiated at the emergency department? A systematic review and meta-analysis PONE-D-23-14334R2 Dear Dr. Wongtanasarasin, 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. An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. 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, Gaetano Santulli, MD Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0289054.r005
Formally Accepted
13 Jul 2023 Acceptance Letter - Gaetano Santulli, Editor PONE-D-23-14334R2 How effective is extracorporeal life support for patients with out-of-hospital cardiac arrest initiated at the emergency department? A systematic review and meta-analysis Dear Dr. Wongtanasarasin: 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. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Professor Gaetano Santulli Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0289054.r006

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