How is depth of anaesthesia assessed in experimental pigs? A scoping review

Alessandro Mirra; Ekaterina Gamez Maidanskaia; Luís Pedro Carmo; Olivier Levionnois; Claudia Spadavecchia

doi:10.1371/journal.pone.0283511

Peer Review History

Original SubmissionOctober 12, 2022
26 Jan 2023 Decision Letter - Silvia Fiorelli, Editor PONE-D-22-28207How is depth of anaesthesia assessed in experimental pigs? A scoping reviewPLOS ONE Dear Dr. Mirra, 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 assess all the reviewers comments Please submit your revised manuscript by Mar 12 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. 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 If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references.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 If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.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. 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 #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: well-conducted review of literature and analyze of different monitors and parameters. Constructive clear discussion to replace the contexte of avoid of awareness and memorization. the work takes place in the background of translational research using pigs Reviewer #2: ABSTRACT Line 45: It should be made clearer that the contrast results are not in relation to how useful the depth of anaesthesia indicators are but to what are the best depth of anaesthesia indicators. Lines 50-51: Maybe the authors should underline the lack of many high quality scientific studies and not only the lack of scientifically valid and reliable indicators of depth anaesthesia in pigs. INTRODUCTION Line 81: Why do they claim that the reliability of the results obtained from translational studies is questioned by the lack of valid depth of anaesthesia indicators? It should be explained in more detail. Lines 87-88: Maybe the answer to this question is already elucidated in the lines 80-81, so the question should not address the usefulness of methodologies to assess DoA in pigs but should refer the best validated ones. Lines 89-91: It is not necessary to describe the differences between a scoping review and a systematic review in the introduction. The authors could explain why they chose a scoping review analysis in the discussion. MATERIAL AND METHODS Lines 170-172: During the data extraction it is very important to know the different quality of the studies evaluated in order to give more emphasis to the high quality studies as well as to show the current gaps in scientific literature. RESULTS Lines 287-288: This result has not been sufficiently clarified, references 11 and 12 are quite different in their methodology and results, hence it should be analysed more in depth. Lines 288: The studies cited, references 11-12-14-16, are not so similar, therefore this statement appears to be incomplete. BIS was compared to different variables with different results and it should be explained accurately. DISCUSSION Lines 364: Perhaps the results about using IOC and PSI indexes should be expressed in detail and discussed. Lines 365-371: The BIS method is evaluated in 8 studies but the authors only discuss 5 out 8; they should also discuss the remaining three studies. Besides, the authors could give some possible reasons for the contrasting results when using the BIS method. ****** 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: Yes: Massimiliano Pelli ******** [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.0283511.r001
Revision 1
9 Feb 2023 Author Response RESPONSE TO REVIEWERS Dear reviewers, First, thank you very much for the time dedicated to our manuscript, as well as for the suggestions made to improve its quality. Please find below the answers to your comments. Reviewer #1: well-conducted review of literature and analyze of different monitors and parameters. Constructive clear discussion to replace the contexte of avoid of awareness and memorization. the work takes place in the background of translational research using pig Thank you, we appreciate it. Reviewer #2: Thank you for the rigorous assessment of our manuscript and the suggestions provided. ABSTRACT Line 45: It should be made clearer that the contrast results are not in relation to how useful the depth of anaesthesia indicators are but to what are the best depth of anaesthesia indicators. Thank you for your comment. Contrasting results have been found in relation to how useful the depth of anaesthesia (DoA) indicators were. We did not find papers specifically analysing which indicator was the best to assess DoA in pigs. The sentence has been modified to clarify better our results. Lines 50-51: Maybe the authors should underline the lack of many high quality scientific studies and not only the lack of scientifically valid and reliable indicators of depth anaesthesia in pigs. Thank you for pointing it out. Due to the nature of the studies found and the type of review chosen, we did not analyse the quality of the papers, but rather screened their results. Our scoping review could be the base for future focused systematic reviews, that could look at the quality of single studies. We added a sentence in the discussion section INTRODUCTION Line 81: Why do they claim that the reliability of the results obtained from translational studies is questioned by the lack of valid depth of anaesthesia indicators? It should be explained in more detail. Thank you for spotting it. A sentence has been added to better explain the concept. The lack of knowledge on how to appropriately assess DoA brings to the difficulty of ensuring a correct DoA. This refers not only to the possible occurrence of intraoperative awareness per se, but also to all the correlated consequences (e.g., cardiovascular, respiratory, hormonal). This brings to the impossibility to differentiate, for example, physiological modifications occurring because of a certain surgical stimulation/treatment from those occurring due to an inappropriate DoA/intraoperative awareness. Lines 87-88: Maybe the answer to this question is already elucidated in the lines 80-81, so the question should not address the usefulness of methodologies to assess DoA in pigs but should refer the best validated ones. This comment has been partially answered above. Unfortunately, in veterinary medicine and especially in pigs, no validated DoA indicators are present (as also shown by the present review). Thus, we did not want to look only for validated DoA indicators, but rather for all the methodologies used in pigs so far. For example, we found that reaction to claw clamp has been widely used as sole DoA indicator, despite being inappropriate for this scope when used alone. Our review highlights how DoA assessment has not been always done in a correct way in pigs, and how really few steps toward a better DoA assessment have been performed in the last decades. Lines 89-91: It is not necessary to describe the differences between a scoping review and a systematic review in the introduction. The authors could explain why they chose a scoping review analysis in the discussion. Thank you for your suggestion. The sentence has been removed from the Introduction and a small paragraph has been added in the discussion section. MATERIAL AND METHODS Lines 170-172: During the data extraction it is very important to know the different quality of the studies evaluated in order to give more emphasis to the high quality studies as well as to show the current gaps in scientific literature. Even if it would be really interesting to analyse the quality of single studies, this was out of the scope of the present review. Unfortunately, the nature of the published papers did not allow us to perform a systematic review (for which a risk of bias assessment is a requirement) and/or to have a homogenous assessment of the quality of single studies. RESULTS Lines 287-288: This result has not been sufficiently clarified, references 11 and 12 are quite different in their methodology and results, hence it should be analysed more in depth. Thank you for your suggestion. We modified the text focusing on the outcome that was of most interest for us, meaning the statistical difference among BIS values at clinically relevant DoA levels (identified in all the studies as MAC and MAC-multiples). Lines 288: The studies cited, references 11-12-14-16, are not so similar, therefore this statement appears to be incomplete. BIS was compared to different variables with different results and it should be explained accurately. Linked to the previous comment: we slightly modified the text to let the reader understand that we took in consideration only the outcome that was in common among studies and of interest for us (statistical difference among DoA levels, identified with MAC and MAC-multiples). DISCUSSION Lines 364: Perhaps the results about using IOC and PSI indexes should be expressed in detail and discussed. Thank you for spotting it. A sentence has been added to provide further information. Lines 365-371: The BIS method is evaluated in 8 studies but the authors only discuss 5 out 8; they should also discuss the remaining three studies. Besides, the authors could give some possible reasons for the contrasting results when using the BIS method. Thank you for your suggestion. We agree with you; the other three studies have been included in the discussion. Possible reasons for the heterogenicity of the results and the unsuitability of BIS in pigs are discussed in the following lines. Attachments Attachment Submitted filename: RESPONSE TO REVIEWERS.docx https://doi.org/10.1371/journal.pone.0283511.r002
9 Mar 2023 Decision Letter - Silvia Fiorelli, Editor How is depth of anaesthesia assessed in experimental pigs? A scoping review PONE-D-22-28207R1 Dear Dr. Mirra, 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, Silvia Fiorelli Academic Editor PLOS ONE Additional Editor Comments : Congratulations to the authors and thanks to the reviewers for the suggestions provided which really helped improve the quality of the manuscript. 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 #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 #1: Yes Reviewer #2: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: 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 #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 #1: Yes 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 #1: The precisions that have been added improve the manuscript. In the abstract, the conflicting results in DoA indicators usefulness appear more clearly. Some studies cited use stimulus-reponse as a DoA indicator evaluation. A short explanation on difference, crucial in humans'care, between awareness and recall and movement to surgical stimulation could be added in the discussion. Minipigs without any study found appear the same way as pigs in the conclusion, I would find better to separate theses different situations with absence of study or absence of proof in the studies Reviewer #2: All my comments were correctly evalueted and analyzed. You did appropriated modifications of the text. ****** 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: Yes: massimiliano pelli ******** https://doi.org/10.1371/journal.pone.0283511.r003
Formally Accepted
14 Mar 2023 Acceptance Letter - Silvia Fiorelli, Editor PONE-D-22-28207R1 How is depth of anaesthesia assessed in experimental pigs? A scoping review Dear Dr. Mirra: 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. Silvia Fiorelli Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0283511.r004

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