Outcomes of mechanically ventilated patients with COVID-19 associated respiratory failure

Christopher S. King; Dhwani Sahjwani; A. Whitney Brown; Saad Feroz; Paula Cameron; Erik Osborn; Mehul Desai; Svetolik Djurkovic; Aditya Kasarabada; Rachel Hinerman; James Lantry; Oksana A. Shlobin; Kareem Ahmad; Vikramjit Khangoora; Shambhu Aryal; A. Claire Collins; Alan Speir; Steven Nathan

doi:10.1371/journal.pone.0242651

Peer Review History

Original SubmissionJuly 13, 2020
18 Aug 2020 Decision Letter - Andrea Ballotta, Editor PONE-D-20-21719 Outcomes of Mechanically Ventilated Patients with COVID-19 Associated Respiratory Failure PLOS ONE Dear Dr. King, 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 Oct 02 2020 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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Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols We look forward to receiving your revised manuscript. Kind regards, Andrea Ballotta Academic Editor PLOS ONE Additional Editor Comments: Thanks for your submission. On the basis of the reviewer's comments i deem the paper not suitable for publication. It needs to be strongly revised. We don't need other partial data. WE need data about medium and long term outcome. The COVID 19 period has also been a sort of nightmare for science. WE must do much better. Journal requirements: When submitting your revision, we need you to address these additional requirements. 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. 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Please see the following video for instructions on linking an ORCID iD to your Editorial Manager account: https://www.youtube.com/watch?v=_xcclfuvtxQ [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: Partly Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 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: Yes 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: Yes 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: Dear authors, Thanks for your manuscript. I strongly belive in your message but unfortunately you referred to partial data, particularly about the patient's outcome. My suggestion is to obtain all patient's outcome, complications and ventilation management data and to revised the manuscript results. Reviewer #2: Thanks for your paper. To be precise in your analysis you might put the following details in the paper. I wuold be important to indicate how much time patients has been treated before intubation ( sintoms, NIV and High flow cannula time). Which was the cutoff for intubation, it was differnt over the time ? When you indicate the ventilation it has been inappropriate only define the ammount of on ml/kg and plateu. Is more convenient to indicate at least the driving pressure or better the compliance oder a partition with esophageal baloon. Which were the indication for ECMo? Murray score Oxigenation index....? And which was the ECMO capability in the number of the admission in ICU . Finally the big limitation you have also underline is the lack of long term survival which is important to evaluate the treatment. ****** 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: Yes:** Mirko Belliato 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. 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Revision 1
8 Sep 2020 Author Response To the Editor, Thanks to both you and your reviewers for your thoughtful and favorable review of our manuscript. We are pleased to provide a revised version for subsequent review. With this revision we will submit a de-identified version of our dataset as requested. We have attempted to answer the reviewers’ comments below. We look forward to your review. Respectfully, Christopher King, MD Reviewer #1: Dear authors, Thanks for your manuscript. I strongly believe in your message but unfortunately you referred to partial data, particularly about the patient's outcome. My suggestion is to obtain all patient's outcome, complications and ventilation management data and to revised the manuscript results. Thank you for your kind words with regards to our manuscript. Initially we hoped to get this manuscript out early to provide information to clinicians with regards to outcomes in intubated COVID-19 patients, but as you point out, a complete data set including all outcomes is more informative. We have now updated all patient outcomes so that all included patients have a clinical outcome of either death or discharge from the hospital. All statistics and tables have been updated in accordance with this change as well. To our knowledge this makes our manuscript the first to report definitive outcomes on an entire cohort of patients with COVID-19 requiring invasive mechanical ventilation. Reviewer #2: Thanks for your paper. To be precise in your analysis you might put the following details in the paper. I wuold be important to indicate how much time patients has been treated before intubation ( sintoms, NIV and High flow cannula time). We include in the manuscript the time from admission to intubation for all included patients. This is provided in the results section where it states: “The average time from admission to intubation was 2.5 days (± 3.0 SD) (Range: 0-18 days); however, 43 patients (26%) were intubated on the day of admission. There was no significant difference in the mean time to intubation between the deceased patients and survivors (2.4 vs. 2.7 days, p = 0.54).” We are unable to provide data on time from symptom onset to intubation. Unfortunately, we are also limited in our ability to report specific data on use of HFNC and NIV. We do mention in the methods section that use of NIV was relatively uncommon. We have added a statement in the limitations section to address this. See the next comment for what was added. Which was the cutoff for intubation, it was differnt over the time ? Very early on we had a low threshold for intubation but quickly evolved to a strategy of delayed intubation and reliance on HFNC. The vast majority of patients would have been managed with a greater reliance on HFNC. We added the following to the limitations section “Another issue is that we were unable to provide specific data on use of HFNC or NIV prior to intubation. As mentioned in the methods, our center evolved to a strategy of delayed extubation and aggressive HFNC support relatively early in our surge, although our pre-intubation management strategy was somewhat in flux over time.” When you indicate the ventilation it has been inappropriate only define the ammount of on ml/kg and plateu. Is more convenient to indicate at least the driving pressure or better the compliance oder a partition with esophageal baloon. Patients often had multiple changes in their ventilator settings as their clinical status progressed and had evolving lung compliance over time. Given this we found it difficult to report specifics on ventilator or lung compliance in a manner that we thought would be instructive to providers. We do believe that our ventilator management across the system was consistent with current best practices and would be similar to standard of care ventilator management in similarly structured hospital systems. Our key message in writing the manuscript is to provide information on outcomes of mechanically ventilated patients rather than to attempt to provide guidance on specific ventilator management strategies. We have added a section to the limitations portion of the paper to highlight these issues. It reads “Finally, since patients frequently had evolving physiology with variable lung compliance and ventilator settings, we are unable to provide specific details on these parameters. However, our ventilator management was in keeping with current best practices and therefore we believe that our survival estimates would be reproducible in similar health care systems.” No patients had esophageal balloons placed given concerns for staff exposure to COVID-19. Which were the indication for ECMo? Murray score Oxigenation index....? And which was the ECMO capability in the number of the admission in ICU . Our indications for ECMO initiation were in line with those recommended by ELSO. As stated in the text “Patients were considered for venovenous (VV) ECMO if age < 60 years old, on IMV < 10 days, had a P/F ratio < 100 and/or failed lung protective ventilation, despite neuromuscular blockade and prone positioning, or had recalcitrant hypercapnic acidosis affecting perfusion.” Like many other clinical decisions, ECMO was initiated only after a formal consultation by an experience ECMO intensivist and discussion with the cannulating cardiac surgeon. We were not reliant on a single parameter but did require all patients to fail conventional lung protective ventilation, neuromuscular blockade and proning. We expanded our typical ECMO capacity to the point that we were staffing up to 10 ECMO patients simultaneously. This is an increase from our typical maximum capacity of approximately 6 patients. Finally the big limitation you have also underline is the lack of long term survival which is important to evaluate the treatment. Thank you for raising this important point. As mentioned above, we have updated outcomes for all patients included in the study. This makes our manuscript unique as it is one of the only studies providing complete outcomes data for critically ill COVID-19 patients. https://doi.org/10.1371/journal.pone.0242651.r002
9 Nov 2020 Decision Letter - Chiara Lazzeri, Editor Outcomes of Mechanically Ventilated Patients with COVID-19 Associated Respiratory Failure PONE-D-20-21719R1 Dear Dr. King, 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, Chiara Lazzeri Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation. Reviewer #2: All comments have been addressed ******** 2. 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 #2: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #2: Yes ****** 4. 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 #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 #2: Yes ****** 6. 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 #2: Thanks Can you please put in the paper ECMO cannulation parameters you have indicated on the answer ? ****** 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 #2: No https://doi.org/10.1371/journal.pone.0242651.r003
Formally Accepted
12 Nov 2020 Acceptance Letter - Chiara Lazzeri, Editor PONE-D-20-21719R1 Outcomes of Mechanically Ventilated Patients with COVID-19 Associated Respiratory Failure Dear Dr. King: 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 Dr. Chiara Lazzeri Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0242651.r004

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