Intravenous versus inhalational maintenance of anesthesia for quality of recovery in adult patients undergoing non-cardiac surgery: A systematic review with meta-analysis and trial sequential analysis

Min Shui; Ziyi Xue; Xiaolei Miao; Changwei Wei; Anshi Wu

doi:10.1371/journal.pone.0254271

Peer Review History

Original SubmissionNovember 11, 2020
11 Jan 2021 Decision Letter - Ahmed Negida, Editor PONE-D-20-35422 Intravenous versus inhalational maintenance of anesthesia for quality of recovery in adult patients: a systematic review with meta-analysis and trial sequential analysis PLOS ONE Dear Dr. Wu, 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 Feb 22 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, Ahmed Negida, MD Academic Editor PLOS ONE Journal Requirements: When submitting your revision, we need you to address these additional requirements. 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. 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 include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information. 3. Please include your tables as part of your main manuscript and remove the individual files. Please note that supplementary tables (should remain/ be uploaded) as separate "supporting information" files. [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: The authors conducted a meta-analysis with trial sequential analysis to determine if total intravenous anesthesia was better than inhalation anesthetics in global recovery of patients. The clinical trials included in this meta-analysis used Quality of Recovery-40 score (QoR 40). The primary studies mostly involved mostly females, patients undergoing outpatient or ambulatory surgeries, intermediate to low risk surgeries. This is an important question for anesthesiologist, which to date has generated inconclusive results. This study attempts to combine results from nine studies and in essence reaches the same conclusion that the results are inconclusive. General Comments 1. Though the total number of studies is 9 and n=922 patients, in reality there are two types of studies. One group of studies reporting results by six hours which has n of 193 and a second group reporting results by postoperative day one with an n= 839. The smaller group shows some benefit of total intravenous anesthesia, but the larger group does not show a difference in global recovery as reported by by QoR 40 score. Both groups do not achieve RIS threshold, so based on trial sequential analysis one can consider that the meta-analysis is under-powered to date. 2. All studies did not report all domains and sub-analysis of domains contain even less number of patients, which highlight another limitation of the study. 3. Trial Sequential analysis have their own limitations and it may be helpful for readers if the authors highlight those limitations (see Anaesthesia 2020, 75, 15-20) and explain how they have addressed some of the methodological limitation of the study. 4. This study provides a framework for future studies and I suspect, as with many meta-analyses, this is probably one of the initial ones in preparation for other analysis in future. 5. In my opinion considering that the studies showing benefit of total intravenous anesthesia are limited to six hours and have less than 200 patients, it would be advisable to tone down the benefit of total intravenous anesthesia versus inhalational anesthetic and highlight more than methodology, it's limitations and inconclusive nature of this question so far. 6. Another point to highlight is that the difference in absolute score is very small and its clinical significance is not clear. Specific comments P4 L71: What is meant by ‘quality of healthcare resources”? P4 L81: …’discomfort’ sounds very informal. May be authors may consider ‘ …. various factors impact quality of recovery of patients after surgery. ‘ Figure 4: Post-operative Day 1 Physical independence The total n should be 229 and 225. Please amend. Reviewer #2: Title: Intravenous versus inhalational maintenance of anesthesia for quality of recovery in adult patients Suggested: Intravenous versus inhalational maintenance of anesthesia for quality of recovery in adult patients undergoing non-cardiac surgery. Abstract: Background: Second line: It is still controversial as to which technique Suggested: It is still controversial which technique Third line: This meta-analysis aimed to compare impact Suggested: This meta-analysis aimed at comparing the impact Methods: Line 8/9: estimated required information size for total QoR-40 scores were not surpassed by recovered evidence in our meta-analysis Suggested: estimated required information size for total QoR-40 scores was not surpassed by recovered evidence in our meta-analysis. Page 5 All relevant data are within the manuscript and its Supporting Information files. Suggested: All relevant data are within the manuscript and its supporting information files Body of manuscript: Line 25: It is still controversial as to which technique Suggested: It is still controversial which technique Line 26: This meta-analysis aimed to compare impact Suggested: this meta-analysis aimed at comparing the impact Line 69: The introduction mentioned (ambulatory anaesthesia) while the title is not about ambulatory anaesthesia??! Line 80: Please, omit reference number 7 and omit it from the references list as it is related to paediatric anaesthesia and the scope of the manuscript is adult anaesthesia. Line 127: Kindly, (Supplementary) to be written as (supplementary) Line 132/133: Here the 9 included studies used the intravenous induction route so the manuscript compares TIVA with inhalational maintenance, so inhalational induction should be omitted. Line 258: Kindly, change (Supplementary) to be (supplementary). Discussion: Lines 298/299: more evidence is needed for a firm conclusion. Then we need to consider the clinical significance. Suggested: more evidence is needed for a firm conclusion, then we need to consider the clinical significance. Line 309: It might due to the mean difference (95% CI) too close to the invalid line Suggested: It might be due to the mean difference (95% CI) was too close to the invalid line Line 333: meta-analysis to address patient perception of postoperative recovery quality between the two anaesthetic techniques. Suggested: meta-analysis to address patient perception of postoperative quality of recovery of the two anaesthetic techniques. Line 344: participants of most studies were female Suggested: participants of most studies were females Line 354: And including these studies in future review updates would increase certainity of the effect. Suggested: And including these studies in future review updates will increase certainity of the effect. References: Reference number 19 link is invalid ****** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review?** For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: No Reviewer #2: No [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0254271.r001
Revision 1
4 Feb 2021 Author Response General Comments 1. Though the total number of studies is 9 and n=922 patients, in reality there are two types of studies. One group of studies reporting results by six hours which has n of 193 and a second group reporting results by postoperative day one with an n= 839. The smaller group shows some benefit of total intravenous anesthesia, but the larger group does not show a difference in global recovery as reported by by QoR 40 score. Both groups do not achieve RIS threshold, so based on trial sequential analysis one can consider that the meta-analysis is under-powered to date. From reported evidence, our meta-analysis and trial sequential analysis, it is true that we couldn’t draw a firm conclusion, but it is real and it can provide reference for future research. 2. All studies did not report all domains and sub-analysis of domains contain even less number of patients, which highlight another limitation of the study. We couldn’t agree more. These limitations were discussed in our manuscript. 3. Trial Sequential analysis have their own limitations and it may be helpful for readers if the authors highlight those limitations (see Anaesthesia 2020, 75, 15-20) and explain how they have addressed some of the methodological limitation of the study. It is true that trial sequential analysis (TSA) have their own limitations. The TSA aimed to make the conclusion more reliable. And we complied with its rules. Thus, we think there may be no need to discuss the limitations of TSA in this meta-analysis. 4. This study provides a framework for future studies and I suspect, as with many meta-analyses, this is probably one of the initial ones in preparation for other analysis in future. There seems no requirement for revision in this comment. 5. In my opinion considering that the studies showing benefit of total intravenous anesthesia are limited to six hours and have less than 200 patients, it would be advisable to tone down the benefit of total intravenous anesthesia versus inhalational anesthetic and highlight more than methodology, it's limitations and inconclusive nature of this question so far. Our meta-analysis and TSA results clearly showed that current evidence couldn’t draw a firm conclusion. The current evidence does not support that total intravenous anesthesia is more advantageous. 6. Another point to highlight is that the difference in absolute score is very small and its clinical significance is not clear. In our meta-analysis, trial sequential analysis showed that the difference in absolute score was not established, its clinical significance is certainly not clear. Thus, more evidence is needed. That was our conclusion. Specific comments P4 L71: What is meant by ‘quality of healthcare resources”? We revised it in the manuscript. P4 L81: …’discomfort’ sounds very informal. May be authors may consider ‘ …. various factors impact quality of recovery of patients after surgery. ‘ We revised it in the manuscript. Figure 4: Post-operative Day 1 Physical independence The total n should be 229 and 225. Please amend. The study (De Carli 2020) was not estimable. Thus, the total number is right. Reviewer #2: Title: Intravenous versus inhalational maintenance of anesthesia for quality of recovery in adult patients Suggested: Intravenous versus inhalational maintenance of anesthesia for quality of recovery in adult patients undergoing non-cardiac surgery. We revised it in the manuscript. Abstract: Background: Second line: It is still controversial as to which technique Suggested: It is still controversial which technique We revised it in the manuscript. Third line: This meta-analysis aimed to compare impact Suggested: This meta-analysis aimed at comparing the impact We revised it in the manuscript. Methods: Line 8/9: estimated required information size for total QoR-40 scores were not surpassed by recovered evidence in our meta-analysis Suggested: estimated required information size for total QoR-40 scores was not surpassed by recovered evidence in our meta-analysis. We revised it in the manuscript. Page 5 All relevant data are within the manuscript and its Supporting Information files. Suggested: All relevant data are within the manuscript and its supporting information files We revised it in the manuscript. Body of manuscript: Line 25: It is still controversial as to which technique Suggested: It is still controversial which technique We revised it in the manuscript. Line 26: This meta-analysis aimed to compare impact Suggested: this meta-analysis aimed at comparing the impact We revised it in the manuscript. Line 69: The introduction mentioned (ambulatory anaesthesia) while the title is not about ambulatory anaesthesia??! Line 80: Please, omit reference number 7 and omit it from the references list as it is related to paediatric anaesthesia and the scope of the manuscript is adult anaesthesia. We revised it in the manuscript. Line 127: Kindly, (Supplementary) to be written as (supplementary) We revised it in the manuscript. Line 132/133: Here the 9 included studies used the intravenous induction route so the manuscript compares TIVA with inhalational maintenance, so inhalational induction should be omitted. We revised it in the manuscript. Line 258: Kindly, change (Supplementary) to be (supplementary). We revised it in the manuscript. Discussion: Lines 298/299: more evidence is needed for a firm conclusion. Then we need to consider the clinical significance. Suggested: more evidence is needed for a firm conclusion, then we need to consider the clinical significance. We revised it in the manuscript. Line 309: It might due to the mean difference (95% CI) too close to the invalid line Suggested: It might be due to the mean difference (95% CI) was too close to the invalid line We revised it in the manuscript. Line 333: meta-analysis to address patient perception of postoperative recovery quality between the two anaesthetic techniques. Suggested: meta-analysis to address patient perception of postoperative quality of recovery of the two anaesthetic techniques. We revised it in the manuscript. Line 344: participants of most studies were female Suggested: participants of most studies were females We revised it in the manuscript. Line 354: And including these studies in future review updates would increase certainity of the effect. Suggested: And including these studies in future review updates will increase certainity of the effect. We revised it in the manuscript. References: Reference number 19 link is invalid We coped the link to the browser and opened it. It is right and valid. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0254271.r002
30 Apr 2021 Decision Letter - Ahmed Negida, Editor PONE-D-20-35422R1 Intravenous versus inhalational maintenance of anesthesia for quality of recovery in adult patients undergoing non-cardiac surgery: a systematic review with meta-analysis and trial sequential analysis PLOS ONE Dear Dr. Wu, 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 Jun 14 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, Ahmed Negida, MD Academic Editor PLOS ONE [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 #2: (No Response) Reviewer #3: (No Response) Reviewer #4: All comments have been addressed ******** 2. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #2: Yes Reviewer #3: No Reviewer #4: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #2: Yes Reviewer #3: Yes Reviewer #4: Yes ****** 4. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #2: Yes Reviewer #3: No Reviewer #4: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #2: Yes Reviewer #3: No Reviewer #4: Yes ****** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #2: Comments: 1- Line 69 and 70: Requirement for effectiveness and efficiency of healthcare resources prompts anesthesiologists to consider techniques that provide fast and high quality of recovery. Suggested (kindly, observe that there are 2 suggested changes in the statement) The requirement for effectiveness and efficiency of healthcare resources prompts anesthesiologists to consider techniques that provide a fast and high quality of recovery. 2- Page 4 line 80 and 81: In recent years researchers have recognized the limitations of the fragmentary measures.... Suggested: In recent years, researchers have recognized the limitations of the fragmentary measures... 3- Please, review the tables in page 12 and 13, the reference numbers are different from the numbers of the references written at the end of the manuscript. 4- Line 313/314: It might due to the mean difference (95% CI) was too close to the invalid line suggested: It might be due to the mean difference (95% CI) was too close to the invalid line 5- Line 323: there is an extra space just before the word Herling, please omit this extra space. Reviewer #3: Thank you for the opportunity to review the metanalysis entitled " Intravenous versus inhalational maintenance of anesthesia for quality of recovery in adult patients undergoing non-cardiac surgery: a systematic review with meta-analysis and trial sequential analysis" 1) The premise of the analysis is interesting. However, there are concerning points that may/may not be fixable at this point. Important or possibly contentious question: 2) The included studies differ in the time of outcomes analysis - in the majority - smaller sized studies favored TIVA (are ambulatory/short outcome measure time) in addition represent inadequate work in this domain whereas other relatively larger studies showed “no effect”- plus studies are primarily female gender predominant together making it non-reproducible and more susceptible to selection bias. he problem with this analysis — in theory, you can select the trials you want to include and add them to come up with a number, but the question here is -would the average number apply to these diverse interventions which were compared with user-variable, by using different definitions of outcomes. 3) Introduction: Authors did not justify the rationale of the study. The logic "Wanders" and practically ends in the middle of a thought. Why do authors think that a metanalysis is necessary? Please explain the gaps of knowledge in introduction. 4) Very likely that your analysis is not powered to answer this question. I am sure you will agree that the standards for metanalysis should be higher in such questions due to possible impact on the varying clinical practice and choice of anesthetic agents. The ‘required information size’ necessary to account for heterogeneity and multiple comparisons when the RCTs are added, the necessary TSA boundaries are not reached. Moreover, power should be defined apriori. 5) Please add power analysis and sample size calculation. 6) After reading the conclusion, some may overinterpret the results--therefore avoid making any strong statements and include—"future research is likely to have an important impact." 7) Authors stated the conclusions “strongly” when in fact nothing can be concluded so far for sure. They do have a signal but the results remain inconclusive; considering limitations as discussed above in point 1 and 2. At most the authors should state the “results are inconclusive due to limited power” 8) It would be helpful if you show the results of sensitivity analysis. Please clarify what are duplicate studies? 9) Please include the time period of your search, your last search date, and last metanalysis done. 10) Please name the random effect model used or cite the exact model. 11) Non-cardiac surgeries in title may be a bit misleading. Non-cardiac surgeries can vary a lot with all respect. Authors should consider mentioning something like “Same-day surgeries” 12) Discussion: Similar to introduction. Too wordy and not focused to results. I would suggest reframing it according to the obtained results and just reporting the facts focused on the analysis. Plus, various confusing sentence wording and run-on sentences exist that should be restructured throughout. Awkward phrasing throughout the manuscript detracts from the overall quality of the manuscript. Limitation section should be a thoughtful list that caution your results. Reviewer #4: The manuscript was good and can be accepted Introduction was good written Materials and Methods were good written Results were clear Discussion was good written ****** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #2: No Reviewer #3: No Reviewer #4: Yes:** Mustafa Abd El Raouf [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.0254271.r003
Revision 2
27 May 2021 Author Response Reviewer #2: Comments: 1- Line 69 and 70: Requirement for effectiveness and efficiency of healthcare resources prompts anesthesiologists to consider techniques that provide fast and high quality of recovery. Suggested (kindly, observe that there are 2 suggested changes in the statement) The requirement for effectiveness and efficiency of healthcare resources prompts anesthesiologists to consider techniques that provide a fast and high quality of recovery. We revised it in the manuscript. 2- Page 4 line 80 and 81: In recent years researchers have recognized the limitations of the fragmentary measures.... Suggested: In recent years, researchers have recognized the limitations of the fragmentary measures... We revised it in the manuscript. 3- Please, review the tables in page 12 and 13, the reference numbers are different from the numbers of the references written at the end of the manuscript. We revised it in the manuscript. 4- Line 313/314: It might due to the mean difference (95% CI) was too close to the invalid line suggested: It might be due to the mean difference (95% CI) was too close to the invalid line We revised it in the manuscript. 5- Line 323: there is an extra space just before the word Herling, please omit this extra space. We revised it in the manuscript. Reviewer #3: Thank you for the opportunity to review the metanalysis entitled " Intravenous versus inhalational maintenance of anesthesia for quality of recovery in adult patients undergoing non-cardiac surgery: a systematic review with meta-analysis and trial sequential analysis" 1) The premise of the analysis is interesting. However, there are concerning points that may/may not be fixable at this point. Important or possibly contentious question: 2) The included studies differ in the time of outcomes analysis - in the majority - smaller sized studies favored TIVA (are ambulatory/short outcome measure time) in addition represent inadequate work in this domain whereas other relatively larger studies showed “no effect”- plus studies are primarily female gender predominant together making it non-reproducible and more susceptible to selection bias. he problem with this analysis — in theory, you can select the trials you want to include and add them to come up with a number, but the question here is -would the average number apply to these diverse interventions which were compared with user-variable, by using different definitions of outcomes. We agree with these limitations. We conducted the present meta-analysis also due to these controversies. And we just combined data with similar time point. 3) Introduction: Authors did not justify the rationale of the study. The logic "Wanders" and practically ends in the middle of a thought. Why do authors think that a metanalysis is necessary? Please explain the gaps of knowledge in introduction. We revised it in the last paragraph in introduction. 4) Very likely that your analysis is not powered to answer this question. I am sure you will agree that the standards for metanalysis should be higher in such questions due to possible impact on the varying clinical practice and choice of anesthetic agents. The ‘required information size’ necessary to account for heterogeneity and multiple comparisons when the RCTs are added, the necessary TSA boundaries are not reached. Moreover, power should be defined apriori. There seems no requirement for revision in this comment. 5) Please add power analysis and sample size calculation. The estimated required information size (RIS) in TSA results was sample size calculation. 6) After reading the conclusion, some may overinterpret the results--therefore avoid making any strong statements and include—"future research is likely to have an important impact." We revised it in the manuscript. 7) Authors stated the conclusions “strongly” when in fact nothing can be concluded so far for sure. They do have a signal but the results remain inconclusive; considering limitations as discussed above in point 1 and 2. At most the authors should state the “results are inconclusive due to limited power” We revised it in the manuscript. 8) It would be helpful if you show the results of sensitivity analysis. Please clarify what are duplicate studies? We showed the summarized results and alterations of sensitivity analysis. In the sensitivity analysis, we alternated meta-analytic effects model and excluded each study sequentially in score of each dimension. The results included too much single figures, so we did not upload these figures. If there is a need, we can submit the figures for supplementary files. 9) Please include the time period of your search, your last search date, and last metanalysis done. It showed in the “Search Strategy and Study Selection” part. 10) Please name the random effect model used or cite the exact model. We revised it in the manuscript. 11) Non-cardiac surgeries in title may be a bit misleading. Non-cardiac surgeries can vary a lot with all respect. Authors should consider mentioning something like “Same-day surgeries” We had considered the problem, but not all studies included in our meta-analysis were ‘same-day surgeries’. When we registered the meta-analysis, we did plan to perform a meta-analysis about non-cardiac surgeries. 12) Discussion: Similar to introduction. Too wordy and not focused to results. I would suggest reframing it according to the obtained results and just reporting the facts focused on the analysis. Plus, various confusing sentence wording and run-on sentences exist that should be restructured throughout. Awkward phrasing throughout the manuscript detracts from the overall quality of the manuscript. Limitation section should be a thoughtful list that caution your results. We revised it in the manuscript. Attachments Attachment Submitted filename: Response to Reviewers2.docx https://doi.org/10.1371/journal.pone.0254271.r004
9 Jun 2021 Decision Letter - Martina Crivellari, Editor PONE-D-20-35422R2 Intravenous versus inhalational maintenance of anesthesia for quality of recovery in adult patients undergoing non-cardiac surgery: a systematic review with meta-analysis and trial sequential analysis PLOS ONE Dear Dr. Wu, 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: Thank you for your submission. There are some minor questions for you. In the last revision you haven't addressed all the modifications requested. Please provide to make the paper suitable for publication. Please submit your revised manuscript by June 23rd. 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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: 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. 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Suggested (kindly, observe that there are 2 suggested changes in the statement) The requirement for effectiveness and efficiency of healthcare resources prompts anesthesiologists to consider techniques that provide a fast and high quality of recovery. We revised it in the manuscript. Originally in the last revision, I put the same comment, however you responded to one change only which is the addition of (The) to the start of the statement. There was another change which is the addition of (a) before (fast and high quality of recovery.). Reviewer #4: The manuscript was s good Introduction was good written and including the aim of the study Materials and Methods were good written Results were good written and illustrated Discussion was good written ****** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review?** For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #2: No Reviewer #4: No [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0254271.r005
Revision 3
16 Jun 2021 Author Response We added (a) before (fast and high quality of recovery). Attachments Attachment Submitted filename: response to reviewer3.docx https://doi.org/10.1371/journal.pone.0254271.r006
24 Jun 2021 Decision Letter - Martina Crivellari, Editor Intravenous versus inhalational maintenance of anesthesia for quality of recovery in adult patients undergoing non-cardiac surgery: a systematic review with meta-analysis and trial sequential analysis PONE-D-20-35422R3 Dear Dr. Wu, 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, Martina Crivellari Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0254271.r007
Formally Accepted
29 Jun 2021 Acceptance Letter - Martina Crivellari, Editor PONE-D-20-35422R3 Intravenous versus inhalational maintenance of anesthesia for quality of recovery in adult patients undergoing non-cardiac surgery: a systematic review with meta-analysis and trial sequential analysis Dear Dr. Wu: 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. Martina Crivellari Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0254271.r008

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