PONE-D-25-06871Peripheral Line for Vasopressor Administration: Prospective multicenter Observational Cohort study for survival and safetyPLOS ONE

Dear Dr. Assefa Gemechu,

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 May 08 2025 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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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,

Kamal Sharma

Academic Editor

PLOS ONE

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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. 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. Thank you for stating the following financial disclosure:

The funding for this research was acquired from Addis Ababa University, College of Health Sciences Research grant

Please state what role the funders took in the study. If the funders had no role, please state: "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript."

If this statement is not correct you must amend it as needed.

Please include this amended Role of Funder statement in your cover letter; we will change the online submission form on your behalf.

3. Your ethics statement should only appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please delete it from any other section.

4. We note that you have indicated that there are restrictions to data sharing for this study. For studies involving human research participant data or other sensitive data, we encourage authors to share de-identified or anonymized data. However, when data cannot be publicly shared for ethical reasons, we allow authors to make their data sets available upon request. For information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions.

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Additional Editor Comments :

Hello,

Thanks for assigning this paper for my review. I agree with both reviewers that though science intended is great but it lacks on 3 important aspect and needs major revision viz. Retrospective nature, lack of control arm and statistical analysis needs to be looked into. Despite 1 reviewer suggesting rejection I want to be fair to the authors to address these concerns if they can aptly act on the same.

Methodological Considerations: The study lacks a control group (e.g., patients receiving vasopressors via central venous catheters), which limits causal interpretations. This should be explicitly acknowledged as a limitation. The sample size calculation requires further justification, including a power analysis to confirm its adequacy. The high mortality rate (57.6%), particularly in septic shock (67.8%), is significantly higher than in prior studies. The analysis should better account for confounding factors such as ICU care quality and time to vasopressor initiation.

Statistical and Data Availability Issues: Confidence intervals (CIs) are not consistently reported for hazard ratios, which impacts the interpretation of findings. Effect size measures should be included to assess clinical relevance. Data are not fully available, as required by PLOS ONE. The authors should consider depositing the dataset in a public repository.

Thanks

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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: Partly

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

Reviewer #1: No

Reviewer #2: N/A

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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

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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

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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: As an intensivist myself, I do thank you for this valuable study addressing the safety of peripheral venous catheter administration of vasopressors in circulatory shock patients. Your multicenter prospective approach provides important insights, and the use of Kaplan-Meier and Cox regression analysis strengthens the statistical methodology. However, several areas require improvement to enhance the clarity, rigor, and reproducibility of the findings.

Methodological Considerations: The study lacks a control group (e.g., patients receiving vasopressors via central venous catheters), which limits causal interpretations. This should be explicitly acknowledged as a limitation. The sample size calculation requires further justification, including a power analysis to confirm its adequacy. The high mortality rate (57.6%), particularly in septic shock (67.8%), is significantly higher than in prior studies. The analysis should better account for confounding factors such as ICU care quality and time to vasopressor initiation.

Statistical and Data Availability Issues: Confidence intervals (CIs) are not consistently reported for hazard ratios, which impacts the interpretation of findings. Effect size measures should be included to assess clinical relevance. Data are not fully available, as required by PLOS ONE. The authors should consider depositing the dataset in a public repository.

Language and Clarity: The manuscript contains grammatical errors and inconsistent verb tenses, particularly in the Methods section. A thorough language revision is recommended.

Conclusions: The conclusion that PVC administration is safe should be moderated, as extravasation occurred after 5 days of use. The discussion should clarify potential safe time limits for PVC use.

Overall, this study contributes valuable data to critical care medicine. Addressing these concerns will further strengthen its impact and reliability.

Thank you for your efforts in conducting and sharing this research.

Reviewer #2: Dear Authors,

I do not entirely understand what was your original concept to prove or "rule out". Also, the retrospective manner of the analysis most probably prevented you to reach meaningful comperisons between different patient or procedure groups.

Sincerely

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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

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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.

PONE-D-25-06871R1Peripheral Line for Vasopressor Administration: Prospective multicenter Observational Cohort study for survival and safetyPLOS ONE

Dear Dr. Assefa Gemechu,

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 18 2025 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,

Kamal Sharma

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.

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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 #1: (No Response)

Reviewer #3: All comments have been addressed

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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 #1: Partly

Reviewer #3: Yes

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

Reviewer #1: No

Reviewer #3: Yes

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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 #1: No

Reviewer #3: 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 #3: Yes

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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 #1: This review builds upon my previous comments. While some improvements have been made, key issues remain insufficiently addressed—particularly regarding methodological transparency, statistical rigor, and clarity of presentation.

1. Methodological Concerns: The absence of a control group (e.g., patients receiving vasopressors via central venous catheters) limits the strength of your conclusions. This limitation should be clearly acknowledged and discussed in greater depth. The sample size calculation requires more detailed justification. Please include a formal power analysis to support the adequacy of your study design.

The reported mortality rates (57.6% overall and 67.8% in septic shock) are significantly higher than in comparable studies. Potential confounding variables, such as ICU resource levels, severity scores, or timing of vasopressor initiation, should be addressed or discussed as possible explanations.

2. Statistical Analysis: Confidence intervals are not consistently reported for all hazard ratios, limiting interpretation of statistical precision. No effect size measures (e.g., absolute risk reduction, NNT) are provided, which would help assess the clinical significance of your findings. The proportional hazards assumption is briefly mentioned, but no diagnostic plots or formal outputs (e.g., Schoenfeld residual test results) are included. Consider providing these in supplementary materials.

3. Data Availability: PLOS ONE requires that data underlying the findings be fully available without restriction. Your current statement indicates data are only available upon request due to privacy concerns. Please consider depositing anonymized data in a public repository or provide a stronger justification aligned with journal policy.

4. Language and Clarity: The manuscript contains grammatical errors, awkward phrasing, and inconsistent use of tense, especially in the Methods section. A thorough language revision by a native English speaker or professional editor is strongly recommended.

5. Conclusions and Interpretation: While the study shows a low rate of extravasation (1.2%), all events occurred after prolonged vasopressor use (>5 days). The current conclusion that PVC use is "safe" should be moderated, and a time limit recommendation (e.g., short-term use) should be explicitly discussed. The potential risks of long-term peripheral administration warrant greater emphasis to guide clinicians effectively.

Final Recommendation: Minor Revision

This study has the potential to make a meaningful contribution to the literature on critical care in low-resource environments. However, the above concerns must be addressed to improve the scientific rigor, reproducibility, and clarity of the manuscript.

Thank you again for your efforts in conducting and sharing this important research.

Reviewer #3: All previous comments are accepted. Below is a comment needs attention.

Comment 1: With respect to data availability, authors stated some limitation, please provide reason and which data are not available.

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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 #3: No

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[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.

Peripheral Line for Vasopressor Administration: Prospective multicenter Observational Cohort study for survival and safety

PONE-D-25-06871R2

Dear Dr. Assefa Gemechu,

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 will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager®  and clicking the ‘Update My Information' link at the top of the page. For questions related to billing, please contact billing support .

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,

Kamal Sharma

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewer #1:

Reviewer #3:

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 #1: All comments have been addressed

Reviewer #3: All comments have been addressed

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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 #1: Yes

Reviewer #3: Yes

**********

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

Reviewer #1: Yes

Reviewer #3: 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 #1: Yes

Reviewer #3: 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 #3: Yes

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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 #1: Thank you for your thoughtful and detailed responses to the previous round of review. I appreciate the improvements you have made to the manuscript, particularly in acknowledging methodological limitations, clarifying the sample size rationale, and strengthening the statistical presentation.

Below is a summary of my assessment of the revised submission:

Methodology and Study Design: The absence of a control group (central venous catheter users) is now more clearly acknowledged and discussed. While this limits causal inference, your clarification improves the transparency of the study design. The sample size justification, based on expected mortality rates and feasibility constraints, is acceptable for an observational cohort study.

2. Mortality and Confounding Factors: The addition of a comparative table and discussion of contextual factors (e.g., ICU capacity, patient severity) provides useful background to interpret the relatively high mortality rates. This section is now more balanced and informative.

3. Statistical Analysis: The inclusion of confidence intervals for hazard ratios improves the interpretability of results. The proportional hazards assumption is addressed, and while no diagnostic plots are provided, the explanation is sufficient for the scope of this study.

4. Data Availability: Shared.

5. Language and Clarity: You state that the manuscript has been revised by a native English speaker. Assuming these edits are reflected in the current version, this issue can be considered resolved.

6. Conclusions: The revised conclusion is appropriately moderated. Emphasizing the safety of PVC use for short-term vasopressor administration, with caution regarding prolonged use, is a fair and evidence-based interpretation of your findings.

Overall, this version of the manuscript reflects substantial improvement and better alignment with scientific reporting standards. Thank you again for your careful attention to reviewer feedback and for contributing this important research.

Reviewer #3: The manuscript titled "Peripheral Line for Vasopressor Administration: Prospective multicenter Observational Cohort study for survival and safety" has now addressed all previous comments. It can be now accepted for publication.

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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 #3: No

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