Intertransverse process block to improve quality of recovery and pain management in cardiac surgery: Protocol for a double-blinded randomized controlled trial

Henry Man Kin Wong; Ranjith Kumar Sivakumar; Wai Tat Wong; Albert Kam Ming Chan; Zion Ho Sum Yeung; Pik Yu Chen; Sherry Tsz Wai Tang; Mandy Hiu Man Chu; Randolph Hung Leung Wong; Kwok Ming Ho

doi:10.1371/journal.pone.0328954

Peer Review History

Original SubmissionJuly 15, 2025
29 Aug 2025 Decision Letter - Regina (Rianne) van Boekel, Editor Dear Dr. WONG, 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 submit your revised manuscript by Oct 13 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. 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'. 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Is the methodology feasible and described in sufficient detail to allow the work to be replicable??> Reviewer #1: Yes Reviewer #2: Yes ****** 4. Have the authors described where all data underlying the findings will be made available when the study is complete??> The PLOS Data policy Reviewer #1: Yes Reviewer #2: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English??> Reviewer #1: Yes Reviewer #2: Yes ****** Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics. You may also provide optional suggestions and comments to authors that they might find helpful in planning their study. Reviewer #1: Thank you for the opportunity to review this interesting and relevant study. I believe the topic has clinical value and the manuscript is overall well written. However, I have several minor suggestions that should be addressed before acceptance: -In a study investigating the effect of a block on chronic pain, it is not entirely clear why Quality of Recovery (QoR) score was chosen as the primary outcome rather than the incidence of chronic pain itself. Please clarify the rationale and ensure alignment between the study aim and outcome selection. -I recommend defining chronic postsurgical pain according to the ICD-11 classification. Suggested reference: Schug SA, Lavand'homme P, Barke A, et al. The IASP classification of chronic pain for ICD-11: chronic postsurgical or posttraumatic pain. Pain. 2019;160(1):45–52. doi:10.1097/j.pain.0000000000001413 -The authors should consider and discuss recent studies specifically addressing the impact of ESP block on chronic pain after cardiac surgery, which are highly relevant: Dost B, Sarıkaya Ozel E, Kaya C, et al. Incidence of chronic postsurgical pain after cardiac surgery and the effect of bilateral erector spinae plane block: a randomized controlled trial. Reg Anesth Pain Med. Published online May 7, 2025. doi:10.1136/rapm-2025-106591 Also suggested references; Yu X, Liu C. Intertransverse process block: A narrative review. J Clin Anesth. 2025;104:111857. doi:10.1016/j.jclinane.2025.111857 Dost B, Karapinar YE, Karakaya D, et al. Chronic postsurgical pain after cardiac surgery: A narrative review. Saudi J Anaesth. 2025;19(2):181–189. doi:10.4103/sja.sja_829_24 -The section currently titled “Ultrasound block placement” could be renamed to a more precise heading, for example “Ultrasound-guided block technique” Reviewer #2: Interesting paper SOme issues should be addressed, although overall a very well written protocol 1) why authors choose to do this study single center? 2) it should be added who will perform the blocks 3) primary and secondary end points should be stated , also because sample size is computed on primary E.P. 4) blinding should be better detailed ****** 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? 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Revision 1
8 Sep 2025 Author Response Reviewer 1 1. In a study investigating the effect of a block on chronic pain, it is not entirely clear why Quality of Recovery (QoR) score was chosen as the primary outcome rather than the incidence of chronic pain itself. Please clarify the rationale and ensure alignment between the study aim and outcome selection Thanks for the insightful feedback. We appreciate reviewer’s concern regarding the selection of primary outcome measure. Both quality of recovery and chronic postsurgical pain are important patient-related outcomes in cardiac surgery. In the absence of data on analgesic efficacy of the intertransverse process block (ITPB) in cardiac surgery, it is a crucial first step in establishing baseline analgesic data for this novel technique. We have selected Quality of Recovery-15 (QoR-15) score at 24 hours postoperatively as our primary outcome measure because it is a reliable, validated metric the captures multidimensional patient experience related to postsurgical recovery. The intensity and quality of early recovery are established predictors of long-term outcomes, including the development of chronic postsurgical pain [1]. Superior analgesia and patient comfort in the immediate postoperative period, as captured comprehensively by the QoR-15, are believed to mitigate the central sensitization and neuroplastic changes that underlie the transition from acute to chronic pain. By establishing the efficacy of ITPB in managing acute pain and improving early recovery, the study provides vital preliminary data that can inform the design and power calculations for subsequent larger trials specifically targeting chronic postsurgical pain as the primary outcome. We have clarified this rationale in the revised manuscript (Lines 457-465) to better highlight the study’s priori role as a foundational investigation for ITPB in cardiac surgery. The title of the manuscript is also revised (Lines 4-6), for both the manuscript and the trial registration, to better align with the aim of the study. Chronic postsurgical pain outcomes at three months and beyond will be analyzed both with and without adjusting for QoR at baseline and in the immediate postoperative period, to account for potential influence of early recovery on chronic postsurgical pain perception (Lines 365-369). References: [1] Maurice-Szamburski A, Bringuier S, Auquier P, Capdevila X. From pain level to pain experience: redefining acute pain assessment to enhance understanding of chronic postsurgical pain. Br J Anaesth. 2024 Nov;133(5):1021-1027. doi: 10.1016/j.bja.2024.08.003 2. I recommend defining chronic postsurgical pain according to the ICD-11 classification. Suggested reference: Schug SA, Lavand'homme P, Barke A, et al. The IASP classification of chronic pain for ICD-11: chronic postsurgical or posttraumatic pain. Pain. 2019;160(1):45–52. doi:10.1097/j.pain.0000000000001413 Thanks for the recommendation. The definition of chronic postsurgical pain in the manuscript text has been revised (Lines 292-294) with the suggested reference included. 3. The authors should consider and discuss recent studies specifically addressing the impact of ESP block on chronic pain after cardiac surgery, which are highly relevant: Dost B, Sarıkaya Ozel E, Kaya C, et al. Incidence of chronic postsurgical pain after cardiac surgery and the effect of bilateral erector spinae plane block: a randomized controlled trial. Reg Anesth Pain Med. Published online May 7, 2025. doi:10.1136/rapm-2025-106591 Also suggested references; Yu X, Liu C. Intertransverse process block: A narrative review. J Clin Anesth. 2025;104:111857. doi:10.1016/j.jclinane.2025.111857 Dost B, Karapinar YE, Karakaya D, et al. Chronic postsurgical pain after cardiac surgery: A narrative review. Saudi J Anaesth. 2025;19(2):181–189. doi:10.4103/sja.sja_829_24 Thanks for the suggestions. The recent study describing the effect of ESP block on chronic pain after cardiac surgery has been included in the manuscript (Lines 143-144) and appropriately cited. The review article on intertransverse process block is also appropriately cited in the manuscript. 4. The section currently titled “Ultrasound block placement” could be renamed to a more precise heading, for example “Ultrasound-guided block technique” Thanks for the comment. The section title has been revised as suggested. Reviewer 2 1. Why author choose to do this study single center? Thank you for the question. A primary reason for doing this study single center is the cost and feasibility. This study is only supported by internal funding from my department. A single center design is therefore significantly less expensive and require fewer resources for administration and coordination, making it a practical choice. There are three cardiac surgical centers in Hong Kong, with slight differences in practice for both surgery and anaesthesia. Moreover, intertransverse process block is a relatively new regional technique that requires training and expertise. By confining the study to one location, we can ensure consistency in clinical practice and staff training. This helps reduce the risk of confounders that can arise from different institutional cultures or techniques, benefiting internal validity, where the observed effects are more likely due to the intervention itself rather than external factors. This is important for a preliminary study without much baseline data from the literature. We acknowledge the limitation of a single-center design in generalizability. We hope to generate initial findings from this study which supports substantiation to a large-scale study in the future. 2. It should be added who will perform the blocks. Thank you for the comment. We have indicated in the “Ultrasound-guided block technique” section that the study intervention will be performed by an experienced anesthesiologist who completed more than fifty successful ITPB procedures and takes no further part in the study. 3. Primary and secondary end points should be stated, also because sample size is computed on the primary E.P. Thank you for the comment. The primary outcome is the Quality of Recovery-15 (QoR-15) score at 24 hours after tracheal extubation. The secondary outcomes include acute pain scores, time to first morphine rescue, patient satisfaction, postoperative morphine requirements, opioid-related side effects, and time to extubate. Chronic pain parameters such as incidence of chronic postsurgical pain, and the pain interferences will be recorded as secondary outcomes. We have specifically highlighted and clearly stated our primary and secondary outcomes in the manuscript. 4. Blinding should be better detailed. Thank you for the comments. The blinding details, including preparation of the randomization envelopes, the study syringes, and the personnels involved in the preparation are revised with better details (Lines 210-215) Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0328954.r002
10 Sep 2025 Decision Letter - Regina (Rianne) van Boekel, Editor Intertransverse process block to improve quality of recovery and pain management in cardiac surgery: protocol for a double-blinded randomized controlled trial PONE-D-25-36620R1 Dear Dr. WONG, We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. For questions related to billing, please contact billing support . If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Regina (Rianne) L.M. van Boekel Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewer #1: Reviewer #2: Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions? Reviewer #1: Yes Reviewer #2: Yes ******** 2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses??> Reviewer #1: Yes Reviewer #2: Yes ****** 3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable??> Reviewer #1: Yes Reviewer #2: Yes ****** 4. Have the authors described where all data underlying the findings will be made available when the study is complete??> The PLOS Data policy Reviewer #1: Yes Reviewer #2: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English??> Reviewer #1: Yes Reviewer #2: Yes ****** Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics. You may also provide optional suggestions and comments to authors that they might find helpful in planning their study. Reviewer #1: The authors have undertaken substantial revisions in response to the reviewers’ and editors’ comments. The manuscript has been considerably improved in terms of clarity, methodological detail, and overall presentation. I would like to congratulate the authors on their efforts and their commitment to enhancing the quality of the work. Reviewer #2: All comments have been addressed and authors should be complimented for performing such a relevant study ****** 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: Fabrizio d'ascenzo ******** https://doi.org/10.1371/journal.pone.0328954.r003
Formally Accepted
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