Effects of Low Load Blood Flow Restriction Training on Post-Surgical Musculoskeletal Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The authors have submitted interesting research titled "Effects of Low Load Blood Flow Restriction Training on Post-surgical Musculoskeletal Patients: A Systematic Review of Randomized Controlled Trials”. The study delves into the advantages and drawbacks of tourniquets over low intensity resistance training, performed using a good quality procedure, and properly reports their work based on the consensus PRISMA. Therefore, based on its depth and complexity, as well as its potential to contribute valuable insights and stimulate scholarly discussion, this topic appears to align well with the journal's overarching objectives and thematic scope. However, several authors have addressed this topic, providing a wide range of information beyond the current review.

In light of this, previous meta-analyses and systematic reviews included studies that were not added to the current systematic review despite being met by the inclusion criteria. Consequently, I have several concerns about the screening process, since said meta-analyses were used to discuss the results and their articles were published in the review windows. That is why I would like to propose additional issues to include in the systematic review to enhance the study's originality and publication potential. To address these issues and improve the quality of the study, I would like to propose the following recommendations.

Expand the search time frame: Broadening the search period to include all relevant studies from their inception to the present would significantly improve the comprehensiveness of the data. This approach ensures that potential valuable studies are not overlooked, thus reducing the likelihood of gaps in research.

Ensure consistency in methodological reporting: The authors need to maintain consistency in describing their methodological procedures. For example, the age inclusion criteria specified in the flow chart do not align with the information presented in Table 1. Clarification is needed: What was the highest age limit for study inclusion? Was it 70 or 75 years? Resolving this inconsistency is vital for transparency and for ensuring that readers and reviewers can accurately interpret the study design and results.

Follow-up on missing information: The authors should explicitly report whether they attempted to contact the corresponding authors of the 20 studies excluded due to missing information. Reaching out to these researchers could potentially recover critical data and improve the reliability of the study. Including a statement about these efforts would also demonstrate thoroughness in addressing data gaps.

Furthermore, conducting a meta-analysis as part of the study could add significant value. In this way, a moderator analysis would be insightful to know the effects of the kind of cuff (i.e. size, valve, material) and training settings (pressure, intensity, length, etc.). They would need to be analysed as moderators of performance, perceived pain, and postoperative recovery. These details could make the study more actionable for practitioners, such as coaches and rehabilitation specialists, and offer new evidence for the field.

Incorporating these suggestions could enhance the originality of the article and increase its practical relevance and publication potential. It is a strong foundation and, with these adjustments, the study could make an even more meaningful contribution.

Author Response

First of all, we are very grateful to the reviewer for the careful reading of our manuscript and the constructive criticism. Our responses are written below (they are given in a point-by-point manner) and we have included each change in the revised manuscript. All the changes have been highlighted in green in the corrected version of the manuscript.

 

1. Expand the search time frame: Broadening the search period to include all relevant studies from their inception to the present would significantly improve the comprehensiveness of the data. This approach ensures that potential valuable studies are not overlooked, thus reducing the likelihood of gaps in research.

Thank you for your suggestion. We have expanded the search time frame until December 2024. Moreover, we have added information about the origins of blood flow restriction training in the introduction section.

2. Ensure consistency in methodological reporting: The authors need to maintain consistency in describing their methodological procedures. For example, the age inclusion criteria specified in the flow chart do not align with the information presented in Table 1. Clarification is needed: What was the highest age limit for study inclusion? Was it 70 or 75 years? Resolving this inconsistency is vital for transparency and for ensuring that readers and reviewers can accurately interpret the study design and results.

This was amended in the new version of the manuscript; the age limit is 75 years.

3. Follow-up on missing information: The authors should explicitly report whether they attempted to contact the corresponding authors of the 20 studies excluded due to missing information. Reaching out to these researchers could potentially recover critical data and improve the reliability of the study. Including a statement about these efforts would also demonstrate thoroughness in addressing data gaps.

 

Thank you for your comment. We tried to obtain missing data from these excluded studies and had access to the raw data from seven articles (of which only one was considered). Moreover, we also visited the journals’ websites to get access to the auxiliary materials, but we were only successful in one case.  

 

4. Furthermore, conducting a meta-analysis as part of the study could add significant value. In this way, a moderator analysis would be insightful to know the effects of the kind of cuff (i.e. size, valve, material) and training settings (pressure, intensity, length, etc.). They would need to be analysed as moderators of performance, perceived pain, and postoperative recovery. These details could make the study more actionable for practitioners, such as coaches and rehabilitation specialists, and offer new evidence for the field.

Thank you for your relevant suggestion. Accordingly, we have conducted a meta-analysis in which we calculated the overall effect of LLBFRT on each outcome (muscle strength, muscle size, and pain perception). However, considering the total number of studies focused on each outcome, studies’ characteristics (programs’ duration, %AOP used, exercises included, etc.), and, especially, the level of heterogeneity reported, we finally decided not to conduct a moderator analysis since subgroups for analysis need to be well-formed.  

Incorporating these suggestions could enhance the originality of the article and increase its practical relevance and publication potential. It is a strong foundation and, with these adjustments, the study could make an even more meaningful contribution.

Reviewer 2 Report

Comments and Suggestions for Authors

The reviewer has the following concerns about this manuscript:

1. Did the review analyze whether the effects of LLBFRT vary depending on the type of musculoskeletal surgery?

2. How did the quality of evidence and risk of bias, as assessed by the Cochrane Risk-of-Bias Tool (RoB 2) and GRADE-CERQual scale, impact the reliability of the conclusions drawn in the review?

3. How does LLBFRT compare to traditional high-load training (HLT) in terms of mitigating muscle atrophy and weakness during the postoperative rehabilitation of musculoskeletal surgery patients, particularly concerning its impact on muscle strength and volume??

4. How did the inclusion of multiple languages (English, Spanish, and French) and the use of DeCS/MeSH terminologies and synonyms in the search strategy impact the comprehensiveness and potential bias of the study selection process?

5. How does the variation in arterial occlusion pressure (40%, 50%, and 80% AOP) influence the effectiveness of LLBFRT in terms of muscle strength, muscle volume, and pain reduction across the included studies?

6. In the introduction, for the description of musculoskeletal disorders, please reference the up-to-date studies. For example: Accurately and effectively predict the ACL force: Utilizing biomechanical landing pattern before and after-fatigue (https://doi.org/10.1016/j.cmpb.2023.107761)

7. For the conclusion section, please provide some substantive comments or suggestions.

Author Response

First of all, we are very grateful to the reviewer for the careful reading of our manuscript and the constructive criticism. Our responses are written below (they are given in a point-by-point manner) and we have included each change in the revised manuscript. All the changes have been highlighted in green in the corrected version of the manuscript.

 

1. Did the review analyze whether the effects of LLBFRT vary depending on the type of musculoskeletal surgery?

 

Thanks for your question. Our systematic review was not aimed to evaluate the role of musculoskeletal surgery. We used musculoskeletal surgery patients as the target population because our starting hypothesis was that LLBFRT could be effective as an alternative therapy for recovering upper or lower limb functionality.

 

2. How did the quality of evidence and risk of bias, as assessed by the Cochrane Risk-of-Bias Tool (RoB 2) and GRADE-CERQual scale, impact the reliability of the conclusions drawn in the review?

 

Thank you for your relevant question. As it can be read in this new version of the manuscript (Strengthens and Limitations section), the risks of bias reported in most of the articles, as well as the GRADE evaluation conducted on these manuscripts, were assumed as limitations, so the conclusions drawn in our review must be taken in this context.

 

3. How does LLBFRT compare to traditional high-load training (HLT) in terms of mitigating muscle atrophy and weakness during the postoperative rehabilitation of musculoskeletal surgery patients, particularly concerning its impact on muscle strength and volume??

 

Thank you for this question, but our systematic review was not aimed to evaluate this kind of comparison. Nevertheless, considering the overall effect of LLBFRT on the selected outcomes (muscle strength and muscle size) reported by our meta-analysis, it seems that LLBFRT is not a more effective therapy than others (including HLT) performed by control groups.

 

4. How did the inclusion of multiple languages (English, Spanish, and French) and the use of DeCS/MeSH terminologies and synonyms in the search strategy impact the comprehensiveness and potential bias of the study selection process?

 

Thank you for your question. We used only English MeSH terms in our search strategy; from this point, we considered articles written in English, Spanish and French to be selected.

5. How does the variation in arterial occlusion pressure (40%, 50%, and 80% AOP) influence the effectiveness of LLBFRT in terms of muscle strength, muscle volume, and pain reduction across the included studies?

Thank you for your interesting question. We have conducted a meta-analysis in which we calculated the overall effect of LLBFRT on each outcome (muscle strength, muscle size, and pain perception). However, considering the total number of studies focused on each outcome, studies’ characteristics (programs’ duration, %AOP used, exercises included, etc.), and, especially, the level of heterogeneity reported, we finally decided not to conduct a moderator analysis since subgroups for analysis need to be well-formed. 

6. In the introduction, for the description of musculoskeletal disorders, please reference the up-to-date studies. For example: Accurately and effectively predict the ACL force: Utilizing biomechanical landing pattern before and after-fatigue (https://doi.org/10.1016/j.cmpb.2023.107761)

Thank you for your suggestion. We carefully read the manuscript recommended, but we decided not to include it to avoid an excessive focus on ACL injury. 

7. For the conclusion section, please provide some substantive comments or suggestions.

Thank you for your suggestion. This has been amended in the new version of the manuscript. 

Reviewer 3 Report

Comments and Suggestions for Authors

Introduction

 

Paragraph 1

Disorders are not the same as injuries. One of the causes of disorders may be injuries, but not the only one. If the authors write about common injuries, it is worth indicating what it is and what type or muscle. Also, the most common method of treatment is not a very accurate description.

 

Paragraph 2

 

All of the indicated post-operative consequences appear after every intervention in the treatment of the musculoskeletal system. ACL reconstruction is no exception.

 

Please expand the abbreviation AMI.

The development of the indicated consequences is biology, not pathology.

 

Are you sure the authors want to restore strength from the very beginning, e.g. ACL reconstruction? The beginning for the physiotherapy team is the second day after surgery.

 

The argument given by the authors that early restoration of strength will improve functionality. This has nothing to do with gaining functionality. Children do not have much strength, compared to adults, but they have excellent functionality. Patients after a stroke also improve their quality of life without a significant improvement in strength.

 

Results

 

In Table 2

 

There is a lack of complete information regarding the procedure, e.g. it is worth adding which week since the procedure was performed.

 

The Arthroscopy information is not very detailed for the reader, it is worth expanding or removing it.

 

Table 3

 

The description presents (Exercise, Sets and Repetitions) and then the authors present four numerical values ​​in brackets, e.g. (30,15,15,15). It is worth considering a different system.

 

There is a lack of clear information on how the therapeutic results were assessed, e.g. muscle strength or using e.g. EMG.

To compare the effectiveness of exercises, it is worth providing what results were obtained in the control group. For the reader, values ​​such as in the table will easily indicate the analysis and comparison of the effectiveness of the intervention.

 

Discussion

After systematizing the results, it is worth considering implementing them in the discussion. This will increase the value of the manuscript.

Author Response

First of all, we are very grateful to the reviewer for the careful reading of our manuscript and the constructive criticism. Our responses are written below (they are given in a point-by-point manner) and we have included each change in the revised manuscript. All the changes have been highlighted in green in the corrected version of the manuscript.

 

Introduction

Paragraph 1

Disorders are not the same as injuries. One of the causes of disorders may be injuries, but not the only one. If the authors write about common injuries, it is worth indicating what it is and what type or muscle. Also, the most common method of treatment is not a very accurate description.

Thank you for your comment. We have focused on musculoskeletal injuries (located in both upper and lower limbs). Nevertheless, as it is well-known, surgery is often proposed as treatment for these injuries.

Paragraph 2

All of the indicated post-operative consequences appear after every intervention in the treatment of the musculoskeletal system. ACL reconstruction is no exception.

Please expand the abbreviation AMI.

This was amended in the text.

The development of the indicated consequences is biology, not pathology.

We appreciate your comment, but we think biology and pathology are closely related fields, with pathology being a branch of biology that focuses on the study of disease processes.

 

Are you sure the authors want to restore strength from the very beginning, e.g. ACL reconstruction? The beginning for the physiotherapy team is the second day after surgery.

Thank you for your comment. Yes, we are sure. In fact, some selected studies even go so far to include pre-surgery exercise protocols…

 

 

 

The argument given by the authors that early restoration of strength will improve functionality. This has nothing to do with gaining functionality. Children do not have much strength, compared to adults, but they have excellent functionality. Patients after a stroke also improve their quality of life without a significant improvement in strength.

Thank you for your suggestion. We disagree with your opinion since functionality allows us for complex task accomplishment in reaching, prehension, manipulation (upper limb functionality), and locomotion, standing, and supporting body weight (lower limb functionality). We understand that muscle strength plays a key role in all these functions. 

 

Results

In Table 2

There is a lack of complete information regarding the procedure, e.g. it is worth adding which week since the procedure was performed.

Thank you for your suggestion. We tried to include this kind of information in Table 2, but considering the complexity of some training protocols, we decided not to incorporate it to avoid a misconfiguration of this table. 

The Arthroscopy information is not very detailed for the reader, it is worth expanding or removing it.

Thank you for your comment. This was amended.

Table 3 

The description presents (Exercise, Sets and Repetitions) and then the authors present four numerical values ​​in brackets, e.g. (30,15,15,15). It is worth considering a different system.

Thank you for your comment. We have used the same description for training protocols as in the selected manuscripts.

There is a lack of clear information on how the therapeutic results were assessed, e.g. muscle strength or using e.g. EMG.

This was amended in the text.

To compare the effectiveness of exercises, it is worth providing what results were obtained in the control group. For the reader, values ​​such as in the table will easily indicate the analysis and comparison of the effectiveness of the intervention.

Thank you for your comment. We have conducted a meta-analysis in which we calculated the overall effect of LLBFRT on each outcome (muscle strength, muscle size, and pain perception). However, considering the total number of studies focused on each outcome, studies’ characteristics (programs’ duration, %AOP used, exercises included, etc.), and, especially, the level of heterogeneity reported, we finally decided not to conduct a moderator analysis since subgroups for analysis need to be well-formed. 

Discussion

After systematizing the results, it is worth considering implementing them in the discussion. This will increase the value of the manuscript.

This was amended in the new version of the manuscript (discussion section).

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

The reviewers acknowledged the authors' revisions. However, in the first paragraph of the introduction, it is necessary to correct that musculoskeletal injuries occur mainly in the lower extremities, and therefore it is necessary to cite the most recent relevant studies on musculoskeletal injuries in the lower extremities: New insights optimize landing strategies to reduce lower limb injury risk (https://doi.org/10.34133/cbsystems.0126). The author also mentions ACL injuries in the second paragraph. Furthermore, as mentioned by the authors, the bias risk regarding the reporting of the study directly affects the reliability of the study.

Author Response

First of all, we are again very grateful to the reviewer for the careful reading of our manuscript and the constructive criticism. Our response is written below, and we have included each change in the revised manuscript. All these changes have been highlighted in light blue in the new version of the manuscript.

Comments and Suggestions for Authors

The reviewers acknowledged the authors' revisions. However, in the first paragraph of the introduction, it is necessary to correct that musculoskeletal injuries occur mainly in the lower extremities, and therefore it is necessary to cite the most recent relevant studies on musculoskeletal injuries in the lower extremities: New insights optimize landing strategies to reduce lower limb injury risk (https://doi.org/10.34133/cbsystems.0126). The author also mentions ACL injuries in the second paragraph. Furthermore, as mentioned by the authors, the bias risk regarding the reporting of the study directly affects the reliability of the study.

 

Thank you for your comment. After reconsidering your suggestion, we have rewritten the first paragraph and included the recommended manuscript, citing it as [3] in the reference list (by the way, this is a very interesting study).

 

[3] Xu, D., Zhou, H., Quan, W., et al. New Insights Optimize Landing Strategies to Reduce Lower Limb Injury Risk. Cyborg Bionic Syst. 2024; 5:0126. https://doi:10.34133/cbsystems.0126

Reviewer 3 Report

Comments and Suggestions for Authors

Dear Authors,
Thank you for taking my comments into consideration. However, I have a few more comments:

 

MW, MA and AMI can develop rapidly in the postoperative period, and for example, even short periods of immobilization can result in a 20–30% reduction in thigh volume after knee arthroscopy [10]. He emphasizes that the literature cannot be provided with results of “20–30%

Therefore, it is important for physiotherapists to include analytical strength training from the beginning of the rehabilitation process [11, 12], so that the functional recovery period is short
and the quality of life can improve quickly.

Reply to the article Thank you for your comment. Yes, we are sure. In fact, some selected studies go so far as to include preoperative exercise protocols…

Please provide literature confirming the impact, because as a result, there is no information about the occurrence of muscle strength training after anterior cruciate ligament reconstruction.

so that the functional recovery period is short
and the quality of life can improve quickly. Belonging to the task.

Comments on the Quality of English Language

No comments.

Author Response

First of all, we are again very grateful to the reviewer for the careful reading of our manuscript and the constructive criticism. Our response is written below, and we have included each change in the revised manuscript. All these changes have been highlighted in light blue in the new version of the manuscript.

 

Comments and Suggestions for Authors

Dear Authors,

Thank you for taking my comments into consideration. However, I have a few more comments:

MW, MA and AMI can develop rapidly in the postoperative period, and for example, even short periods of immobilization can result in a 20–30% reduction in thigh volume after knee arthroscopy [10]. He emphasizes that the literature cannot be provided with results of “20–30%”.

Thank you for your comment. Although we do not fully understand what is exactly required, we have reviewed again the study published by Wilkinson et al. (2019) [ref. 11 in the new version of our manuscript]. As it can be read in the introduction section, and based on the study of Gerber et al. (2009), muscle size and strength fluctuations are of particular interest when treating injured patients, particularly in the recovery and rehabilitation periods. Even short periods of immobilization or unloading can result in substantial muscle atrophy, with some reports showing 20% to 30% volume reduction within 3 weeks after knee arthroscopy. In fact, after reviewing the study of Gerber et al. (which has been cited as [12] and added to the reference list), quadriceps volume of the involved thigh was 30% less than the uninvolved thigh at 3 weeks post–ACL reconstruction.

 

Wilkinson BG, Donnenwerth JJ, Peterson AR. Use of Blood Flow Restriction Training for Postoperative Rehabilitation. Curr Sports Med Rep. 2019;18(6):224-228. doi:10.1249/JSR.0000000000000604

 

Gerber JP, Marcus RL, Leland ED, Lastayo PC. The use of eccentrically biased resistance exercise to mitigate muscle impairments following anterior cruciate ligament reconstruction: a short review. Sports Health. 2009;1(1):31-38. doi:10.1177/1941738108327531

 

 

 

Therefore, it is important for physiotherapists to include analytical strength training from the beginning of the rehabilitation process [11, 12], so that the functional recovery period is short and the quality of life can improve quickly.

Reply to the article Thank you for your comment. Yes, we are sure. In fact, some selected studies go so far as to include preoperative exercise protocols…

Please provide literature confirming the impact, because as a result, there is no information about the occurrence of muscle strength training after anterior cruciate ligament reconstruction.

Thank you for your comment; we perfectly understand your interest in the early use of strength training after ACL reconstruction because it is also ours.

As you well know, strength training is a key tool to ensure high-quality early-stage rehabilitation. Accordingly to Buckthorpe et al. (2024), the main clinical considerations for early-stage rehabilitation can be grouped into six categories: (1) pain and swelling; (2) joint range of motion (ROM); (3) AMI and muscle strength; (4) movement quality/neuromuscular control during activities of daily living (5) psycho-social-cultural and environmental factors and (6) physical fitness preservation. Thus, if there are no post-surgical complications, these authors also state that it is imperative to minimise the extent of knee extensor weakness during the early-stage post-ACL reconstruction. Moreover, knee extensor maximal and explosive strength 6-weeks post-ACL reconstruction has been shown to predict hop and jump performance 6-months post-ACL surgery (Pua et al., 2017). For these reasons, post-operative strength training should start as soon as possible (first 2-3 weeks post ACL reconstruction).

Following your suggestion, we have rewritten the paragraph you indicated and cites of Buckthorpe [15] and Pua [16] have been added to the text (and also to the reference list).

Buckthorpe M, Gokeler A, Herrington L, et al. Optimising the Early-Stage Rehabilitation Process Post-ACL Reconstruction. Sports Med. 2024;54(1):49-72. doi:10.1007/s40279-023-01934-w

 

Pua YH, Mentiplay BF, Clark RA, Ho JY. Associations Among Quadriceps Strength and Rate of Torque Development 6 Weeks Post Anterior Cruciate Ligament Reconstruction and Future Hop and Vertical Jump Performance: A Prospective Cohort Study. J Orthop Sports Phys Ther. 2017;47(11):845-852. doi:10.2519/jospt.2017.7133

 

…so that the functional recovery period is short and the quality of life can improve quickly. Belonging to the task.

Thank you for your observation. To avoid misunderstandings, we have rewritten this sentence and now it reads as following: “Therefore, it is essential that physical therapists incorporate analytical strength work from the early-stage of the rehabilitation process ​[13, 14]​. Thus, if there are no post-surgical complications, it is imperative to minimise the extent of knee extensor weakness during the early-stage post-ACL reconstruction [15]. Moreover, knee extensor maximal and explosive strength 6-weeks post-ACL reconstruction has been shown to predict hop and jump performance 6-months post-ACL surgery [16]. For these reasons, post-operative strength training should start as soon as possible.