Peer Review History

Original SubmissionDecember 3, 2020
Decision Letter - Vincenzo Lionetti, Editor

PONE-D-20-36884

Comparison of Intravenous Magnesium sulphate and Lidocaine for Attenuation of Cardiovascular Response to Laryngoscopy and Endotracheal Intubation in Elective Surgical Patients at Zewditu Memorial Hospital Addis Ababa, Ethiopia.

PLOS ONE

Dear Dr. Misganaw,

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.

All issues raised by expert reviewers are required.

Please submit your revised manuscript by Mar 07 2021 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: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Vincenzo Lionetti, M.D., PhD

Academic Editor

PLOS ONE

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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: No

Reviewer #2: Partly

Reviewer #3: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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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: Yes

Reviewer #2: Yes

Reviewer #3: 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: No

Reviewer #2: Yes

Reviewer #3: No

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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: PLOS

This study investigates whether the addition of lidocaine or magnesium attenuates increases in heart rate and blood pressure during intubation.

Major comments

- Abstract expected to be revised based on the suggestions below.

- The authors investigate and report both diastolic, mean and systemic blood pressure in great detail besides heart rate. Therefore the article contains a lot of data which makes it more difficult to grasp. I would strongly suggest the authors report heart rate and either systolic or mean arterial pressure in the main text. Other BP data can be provided as a supplement and referred to in the manuscript (e.g.”findings for diastolic and mean arterial pressure were similar, see Supplement XX”).

- A language revision would definitely improve readability of the manuscript.

- p6. Data was collected prospectively. Therefore it is unclear for me why only every second patient was chosen (in order to reach the four month time frame?). Why not every patient, increasing sample size or shortening the study period. Logistic reasons?

- p9. The number of patients in each group should be reported early in the results section (I could only find it in the abstract). Also, since group allocation was based on the anesthetists’ preference, it is quite surprising that group size was so comparable. Please explain.

- When describing results, I suggest to first describe the within-group changes followed by the between-group changes.

- p12. The results for SBP in the text and table 3 differ. Please check (e.g. p value at 5 minutes 0.029 or < 0.001).

- Please describe the incidence of bradycardia and hypotension in the results section and comment in the discussion.

- Discussion. Needs to be heavily restructured and rewritten. Actual numbers need not to be repeated in the discussion section but should be summarized with major findings highlighted. Try to compare the overall results of the study with the overall picture from other reports, not every parameter by itself.

- p22. I am afraid that the study does not support the conclusion that magnesium sulphate is ”better” than lignocaine. Firstly, as the authors touch upon in the discussion, the differences are undoubtedly dose-dependent. Secondly, the use of lidocaine, magnesium or nothing was dependent on the individual anesthetist. Thus other factors such as intubating skills, vaporizer technique etc. could influence the results. In my opinion, the only conclusion to be drawn from the data is rather descriptive: In this setting, with these doses, patients anesthetized by an anesthetist using lidocaine or magnesium had attenuated sympatic responses to intubation, compared to anesthetists using none, with a more pronounced effect in the group given magnesium.

Minor comments

p3. last line: I think increased catecholamines during intubation are a very rare cause of surgical bleeding and renal failure.

p4. The term mean MAP (several instances in the document) is confusing. I would suggest ”MAP”, and specify ”mean + SD” when appropriate.

last line ”at Zewditu ….. Ethiopia.” can be removed.

p5. Remove ””Kirkos sub city district 08”. Remove ”The hospital …July 2018”.

Please describe which difference was deemed significant for the sample size calculation. Also specify assumed means and SD’s based on the Iranian study.

p7. Please explain why opioids such as fentanyl were not used during induction, which to my knowledge would be standard in many parts of the world. Economic reasons? However all patients received tramadol. Is it cheaper than fentanyl?

Were drug doses per kg in actual body weight or ideal body weight.

Was there a specified time frame for injecting lidocaine or magnesium.

P9. Remove ”Following approval …of the hospital”.

Table 1 and elsewhere. It is sufficient to specify the hospital and study period once, this needs not to be repeated in all legends.

Table 1 MAC. At what time point was MAC assessed (it is highly dynamic at the start of anesthesia). Also, are the data presented in intervals? (e.g. below 1%, between 1 and 2%, above 2 %?)

P11. Fourth line. The P-values can be removed, they are already in Table 2.

P12. I would suggest ”SBP” instead of ”mean SBP”

Please describe in methods if/how the p-value was adjusted for multiple comparisons. Since many comparisons are made, a P value of 0.029 is not very convincing, or should it read 0.0029?

Please be consistent in using ”lidocaine” or ”lignocaine” in the document.

Reviewer #2: The topic is very interesting as clinical evidence to reduce cardiovascular response to laryngoscopy and endotracheal intubation especially in patients with CVS problems. You have used the terms lidocaine and lignocaine in different places. Make it uniform even though it is the same drug or justify.

You have said laryngoscopic stimulation has many cardiovascular responses but Does it always reflex cardiovascular response in all settings? What type of cardiovascular response do you expect?

in data collection procedure you have discussed that the study subjects have received the similar care. How do you give similar care for study subjects and who refused to participate in the study since you have no intervention?

Generally the study seems better if conducted with RCT design and your data collection procedure and subject recruitment also favors in that manner. so, it needs clarification on how it can be done to compare those drugs with observational study.

Reviewer #3: The paper covers somewhat an interesting topic and can be appealing for the readership of PLOS ONE. However - although the structure reads with ease - the discussion and conclusion part shall be reworded and rewritten minding to improve clarity and readability. In this regard, I am usually reluctant to question English writing, since I am not a native myself, even though in this case i strongly encourage authors to benefit from a professional/mother tongue English editor.

I do consider the paper publishable pending minor revision, which i resume in the list below for clarity:

1) English revision throughout the paper and in particular in the discussion section.

2) In the Data Collection Procedures section, is not clear at all. In particular explain more in details when, how, and the group description of pretreatment with respective drugs(i.e. Lidocaine, Magnesium, and control group).

3) Also in the Data Collection, it is not sufficiently explained the timing of the delay between drugs assumption and intubation.

4) Further discuss the pro and cons of the sampling method adopted.

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Reviewer #1: Yes: Hans Bahlmann

Reviewer #2: No

Reviewer #3: Yes: Nora Terrasini; MD, PhD

[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.

Revision 1

First of all we would like to say thank you all reviewers for their detailed review. Then let us clear some questions and doubts raised by reviewers

Reviewer 1 (Hans Bahlmann)

1. Why only every second patient was chosen? We used propoablity sampling method (SRS) and the calculation based on systematic random sampling is every second patient.

2. P9. Group allocation is based on anesthetist’s preference? Our data collectors observed and collected data which fulfils the inclusion criteria then if the required number is found in any group before study period is finished they only collected the remain group. E.g. In Lidocaine group the required number reached within 3 months.

3. P12. Table 3 contains p value of between the group and within the group p values. So at 5 min the p value between Group M and Group L is 0.029. and the p value among groups was <0.001

4. P22 our conclusion is based on our finding since the post-hoc analysis shows there is a statistically significance difference between lidocaine and magnesium groups.

Even though the nature of a study design unable to control confounding factors like vaporizers, intubation skill we exclude difficult intubations in the study. And there was no difference among the groups in the type and MAC of inhalational agents.

Minor comment

1. P5. ‘Please describe which difference was deemed significant for the sample size calculation ‘? The Iranian study compared HR, SBP, DBP and MAP. We checked the difference between groups for all parameters and the difference was largest in MAP so we used this one for our sample calculation.

2. P7. Why opioid like fentanyl was not used? In Ethiopia fentanyl was not available in the market and in study setting anesthetists used tramadol.

3. Drug dose was based on actual body weight.

4. Both lidocaine and magnesium were injected before 5 minutes of induction of anesthesia.

5. Table 1 MAC at what time point was MAC assessed? Since the study minutes was short (within 7 minutes) there was no great dynamics and we took the average value within 7 minutes of intubation.

Reviewer2

1. Does cardiovascular reflex always happen in all setting? It may not necessarily in all setting but it happen at least in majority cases.

2. What type of cardiovascular response do you expect? The common ones are tachycardia, hypertension and arrhythmia are common responses to laryngoscopic stimulation.

3. How do you give similar care for study subjects and who refused to participate? We just observed the event and if participants refused we only exclude from study participants otherwise the hospital anesthetists gave similar care for those included and excluded patients. Care was independent of being participant or not.

4. Yes we agreed it is better if it was studied in RCT design, and how you can compare drugs in observational study? Even though it has limitation the hospital practice is somehow favorable for this study design from our previous observation and we tried our best to compare drugs with this study design.

Reviewer 3(Nora Terrasini;MD, PHD)

1. Lidocaine and magnesium sulphate were given before 5 minutes of induction of anesthesia. Both drugs were given in IV push and magnesium sulphate was injected slowly within 5 minutes. After 5 minutes of pretreatment anesthetists induced anesthesia.

Attachments
Attachment
Submitted filename: response for reviewers.docx
Decision Letter - Vincenzo Lionetti, Editor

PONE-D-20-36884R1

Comparison of Intravenous Magnesium sulphate and Lidocaine for Attenuation of Cardiovascular Response to Laryngoscopy and Endotracheal Intubation in Elective Surgical Patients at Zewditu Memorial Hospital Addis Ababa, Ethiopia.

PLOS ONE

Dear Dr. Misganaw,

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.

==============================

ACADEMIC EDITOR: All limitations should be highlighted and discussed.

==============================

Please submit your revised manuscript by May 06 2021 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: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Vincenzo Lionetti, M.D., PhD

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.

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

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 #2: All comments have been addressed

Reviewer #3: 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 #1: No

Reviewer #2: Yes

Reviewer #3: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: 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 #2: Yes

Reviewer #3: 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

Reviewer #3: No

**********

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: Dear authors, thank you for the revised version of the manuscript. It has definitely improved, however my main objection is that I still do not feel that the data fully support the conclusion that magnesium is "better" than lidocaine. Yes there is a difference between the groups but the choice of study drug was based on anaesthetist's preference, thus other factors could explain the results or at least act as confounders.. There was no difference in MAC but MAC at induction is a highly dynamic parameter and thus difficult to measure and compare. At least these issues should be mentioned in the discussion as limitations.

Reviewer #2: You have addressed the concerns raised from reviewers. Thus as my personal opinion this manuscript is suited for publication in this journal.

Reviewer #3: (No Response)

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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

Reviewer #3: 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.

Revision 2

First of all, we would like to acknowledge all reviewers for giving your time to review our manuscript and response letter. Then our responses for reviewers’ comment are put as follow.

Reviewer 1

Dear reviewer!; we accept your concern regarding confounding factors, but we were thinking in observational studies these confounding factors are default and that is why we did not mention. Now we have incorporated the limitation and relevance of the study in the manuscript.

The other concern is ‘the choice of the study drug is by the preference of anesthetist’. In this point what we want to say is the nature of the study is observational and we did not enforce anesthetists to change their plan for the purpose of our study. The data collectors just observe what was happening and collecting data. The study was done in resource limited country, so with it’s limitations we think this study can give information for researchers. Therefore, dear reviewer please review our manuscript for the third time thank you.

Reviewer2

Dear reviewer! Thank you for assuring as we have addressed your comments

Reviewer 3

Dear reviewer! we have tried to rewrite the manuscript with language experts

Attachments
Attachment
Submitted filename: response for reviewers.docx
Decision Letter - Vincenzo Lionetti, Editor

PONE-D-20-36884R2

Comparison of Intravenous Magnesium sulphate and Lidocaine for Attenuation of Cardiovascular Response to Laryngoscopy and Endotracheal Intubation in Elective Surgical Patients at Zewditu Memorial Hospital Addis Ababa, Ethiopia.

PLOS ONE

Dear Dr. Misganaw,

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.

==============================

ACADEMIC EDITOR: some limitations of the study should be added and discussed

==============================

Please submit your revised manuscript by Jun 18 2021 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: http://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,

Vincenzo Lionetti, M.D., PhD

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.

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

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

**********

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: No

Reviewer #3: Yes

**********

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

Reviewer #1: Yes

Reviewer #3: N/A

**********

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

**********

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

**********

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: Dear authors, thank you for adding a discussion of some of the limitations in the discussion section and that you recommend a randomized trial. However I still feel that the conclusion that magnesium is better than lidocaine is not justified, based on my previous arguments. Instead one could write that magnesium was associated with a more favorable hemodynamic response. Also the fact that the study drug was selected by the anesthetist involved should be mentioned in the limitations.

Reviewer #3: (No Response)

**********

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

[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.]

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Revision 3

First of all, we would like to acknowledge all reviewers for giving your time to review our manuscript repeatedly. Then we have tried to reflect our responses as follow for reviewers according to concerns.

Reviewer 1

Dear reviewer! Thank you for your concern to be our article scientifically sounded. And you are not satisfied on our conclusion ‘magnesium is better than lidocaine’. Even though we concluded standing from the statistical analysis we can accept your expression ‘pretreatment of magnesium sulphate is associated with a more favorable hemodynamic response’. For our study design we all are comfortable for this expression and will take it as it is. The other concern is ‘the choice of the study drug is by the preference of anesthetist’. The pushing factor to study on this topic is our clinical observation, anesthetists in our study setting are using these drugs as a prophylaxis but there is a confusion which agent is more preferable than the other. So based on this situation we designed observational cohort to study this topic and we are not sure whether it is limitation or not. But you strongly argued this is the limitation of the study so we have incorporated in the manuscript.

Reviewer 3

Dear reviewer! Thank you for assuring as we have addressed your comments

Attachments
Attachment
Submitted filename: response to reviewers.docx
Decision Letter - Vincenzo Lionetti, Editor

PONE-D-20-36884R3

Comparison of Intravenous Magnesium sulphate and Lidocaine for Attenuation of Cardiovascular Response to Laryngoscopy and Endotracheal Intubation in Elective Surgical Patients at Zewditu Memorial Hospital Addis Ababa, Ethiopia.

PLOS ONE

Dear Dr. Misganaw,

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.

==============================

ACADEMIC EDITOR: please edit the abstract in accord with Reviewer's suggestion

==============================

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Academic Editor

PLOS ONE

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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)

**********

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

**********

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

Reviewer #1: 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

**********

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

**********

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: Dear authors, I feel the main text of the manuscript is now technically sound. Only the abstract needs to be revised reflecting the last changes to the main text. At the moment it still reads that magnesium sulphate is better than lignocaine.

**********

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Reviewer #1: 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.

Revision 4

First of all, we would like to acknowledge reviewer1 for giving your time to review our manuscript repeatedly. Then we corrected the manuscript

Reviewer 1

Dear reviewer! Thank you so much! For reviewing each components of the manuscript carefully. And we have corrected it.

Attachments
Attachment
Submitted filename: Response to Reviewers.docx
Decision Letter - Vincenzo Lionetti, Editor

Comparison of Intravenous Magnesium sulphate and Lidocaine for Attenuation of Cardiovascular Response to Laryngoscopy and Endotracheal Intubation in Elective Surgical Patients at Zewditu Memorial Hospital Addis Ababa, Ethiopia.

PONE-D-20-36884R4

Dear Dr. Misganaw,

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,

Vincenzo Lionetti, M.D., PhD

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 #1: 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 #1: Yes

**********

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

Reviewer #1: 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

**********

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

**********

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: Dear authors, I am fully satisfied with your corrections. Thank you for your perseverance. I also want to congratulate you for your contribution to the science of anesthesia despite having very limited resources.

**********

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

Formally Accepted
Acceptance Letter - Vincenzo Lionetti, Editor

PONE-D-20-36884R4

Comparison of Intravenous Magnesium sulphate and Lidocaine for Attenuation of Cardiovascular Response to Laryngoscopy and Endotracheal Intubation in Elective Surgical Patients at Zewditu Memorial Hospital Addis Ababa, Ethiopia.

Dear Dr. Misganaw:

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

Prof. Vincenzo Lionetti

Academic Editor

PLOS ONE

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