MANUSCRIPT TYPE EVIDENCE-TO-PRACTICE REVIEW 11 Copyright © by Indiana State University Clinical Practice in Athletic Training All rights reserved. ISSN Online 2577-8188 Volume 5 – Issue 2 – September 2022 Safety of Blood Flow Restriction Training for Musculoskeletal Disorders: An Evidence-to-Practice Review Breanna Ferguson, MS, ATC; Erica Schulman, MS, ATC; Matthew Zimmerman, MS, ATC; Zachary K. Winkelmann, PhD, SCAT, ATC University of South Carolina, Columbia, SC ABSTRACT Blood flow restriction training (BFRT) is low-level resistance training while partially occluding proximal blood flow. It is well documented that this style of training leads to increased muscle size as well as strength. It is theorized that these size and strength gains are due in part to the decreased oxygen environment. This results in increased muscular stress without the need for increased external load making this style of resistance training ideal for individuals who have restrictions due to musculoskeletal disorders. The guiding systematic review examined the safety of BFRT when used as a therapeutic intervention for patients with a variety of musculoskeletal disorders. Currently, there are no definitive set of parameters for clinicians to follow to ensure safe and effective use of BFRT. The purpose of the guiding review was to evaluate the safety and possible adverse events that may occur from different BFRT parameters in the rehabilitation or musculoskeletal disorders. There are many different types of devices used when implementing BFRT, but safety parameters suggest using a device that can measure the exact pressure so that occlusion can be personalized for each patient. Using a predetermined pressure for all patients could result in full occlusion, depriving the muscle of all oxygen and creating too much muscular stress. Conversely, not enough occlusion could result in a lack of muscular stress occurring to lead to muscular adaptations, ultimately rendering the treatment pointless. Additionally, timing of the exercises, which is work-to- rest ratios, as well as the frequency of training, is an important component for safe and effective use. Finally, the movement selection, load, and volume contribute to the parameters for safe and effective use of BFRT. Adverse reactions found in the guiding systematic review ranged from discomfort or dull pain to rhabdomyolysis. Following recommended safety guidelines decreased the risk of adverse reactions. Correspondence Dr. Zachary Winkelmann, 1300 Wheat Street, Columbia, SC 29208. E-mail: winkelz@mailbox.sc.edu Twitter: @zachwinkelmann Full Citation Ferguson B, Schulman E, Zimmerman M, Winkelmann ZK. Safety of blood flow restriction training for musculoskeletal disorders: An evidence-to-practice review. Clin Pract Athl Train; 5(2): 11-17. https://doi.org/10.31622/2022/0005.02.3. Submitted: December 7, 2020 Accepted: July 1, 2021. ORIGINAL REFERENCE Minniti MC, Statkevich AP, Kelly RL, et al. The safety of blood flow restriction training as a therapeutic intervention for patients with musculoskeletal disorders: A systematic review. Am J Sports Med. 2020;48(7):1773-1785. doi:10.1177/0363546519882652 SUMMARY CLINICAL PROBLEM AND QUESTION Blood flow restriction therapy (BFRT) is a relatively new therapeutic technique that can be utilized in a variety of musculoskeletal injuries. The guiding systematic review examined 19 studies with eight randomized control trials, seven case report studies, three case series, and one prospective longitudinal quasi-experimental study. Of the eight randomized control studies, four studies diagnosed participants with knee osteoarthritis, three studies of post-surgical anterior cruciate ligament (ACL) reconstruction and non-reconstructive arthroscopy, and a final study on anterior knee pain. This evidence to practice review will discuss the safety and adverse effects associated with all 19 articles, however there will be particular focus placed on the mailto:winkelz@mailbox.sc.edu https://doi.org/10.31622/2022/0005.02.3 Safety of Blood Flow Restriction Training for Musculoskeletal Disorders: An Evidence-to-Practice Review 12 Copyright © by Indiana State University Clinical Practice in Athletic Training All rights reserved. ISSN Online 2577-8188 Volume 5 – Issue 2 – September 2022 randomized control trials of patients with post-surgical ACL reconstruction and non-reconstructive arthroscopy. This is due not only to randomized control trials offering higher levels of evidence than the other study designs, but also due to ACL rupture being a common injury seen in athletic populations. The ACL prevents the tibia from moving anteriorly in relation to the femur. When the ACL is torn, the patient can feel instability with certain motions.1 Surgical repair or reconstruction is sometimes needed to correct the instability. In an 18-month period, 2793 ACL surgeries in Norway were performed at an incidence rate of 85 per 100,000 of those in the main at-risk age group.2 Due to this relatively high incidence rate, ACL rehabilitation is a commonly researched subject with an emphasis being placed on finding increasingly effective therapeutic techniques.1,3 Even with the high incident rate for ACL rupture and reconstruction, there is no gold standard for a specific rehabilitation plan following surgical intervention. Commonly examined factors include time and ability to return to preinjury functional levels. For traditional athletes, ACL rehabilitation can cause them to miss 6-9 months or longer due to rehabilitation needs which can equate to their entire season.4,5 While most patients want a quick return-to-activity, it is the athletic trainer’s responsibility to ensure the knee is able to handle the stresses of returning to high level activity without the risk of performance deficits or reinjury.4 A major consequence of ACL injury and subsequent surgery is thigh muscle atrophy and subsequent strength deficits in the first 12 weeks post-surgery and can remain for over 2 years post operation.6,7 Traditional resistance training requires increasing external load on a muscle resulting in increased muscular stress allowing for hypertrophy and strength adaptations to occur. However, heavy external load is unsafe for an extended period following ACL reconstruction due to graft weakness and overall knee instability. The use of BFRT would allow the patient to provide adequate muscular stress for training adaptations to occur while bypassing the need for heavy external loads. Blood flow restriction therapy is the partial occlusion of blood vessels using a tourniquet or, more commonly, an inflatable cuff around a limb to train a distal muscle using low-level resistance exercises.8 The cuff decreases the amount of oxygen supplied to the muscle which could have detrimental effects if not applied correctly. These detrimental effects can range from mild pain and discomfort to more rare but serious conditions such as rhabdomyolysis (0.008%) and deep vein thrombosis (0.055%).9 Due to the possibility of serious detrimental effects resulting from improper application of BFRT, it is vital to examine the necessary parameters for BFRT that result in the safest application of this therapeutic device. Although use of BFRT does not seem to have adverse side effects when used correctly on adults with musculoskeletal knee conditions, the benefits of the intervention have not been fully examined.10 Therefore, the purpose of this evidence to practice review was to examine the safety and possible adverse events that can occur from different BFRT parameters in order to help guide clinicians in the rehabilitation of patients with musculoskeletal disorders with an emphasis on post-surgical ACL reconstruction.3 SUMMARY OF LITERATURE The authors of the guiding systematic review, Minniti et al., conducted a literature search for articles related to BFRT using MEDLINE, CINAHL, and Embase with a comprehensive list of keywords. The studies had to satisfy the following inclusion criteria: (1) BFRT was the clinical intervention, (2) participants were patients with musculoskeletal system disorders, (3) adverse events are discussed by the authors, (4) studies were published in English, (5) all subjects were human. Exclusion criteria included systematic or narrative reviews. Safety of Blood Flow Restriction Training for Musculoskeletal Disorders: An Evidence-to-Practice Review 13 Copyright © by Indiana State University Clinical Practice in Athletic Training All rights reserved. ISSN Online 2577-8188 Volume 5 – Issue 2 – September 2022 The literature search yielded 5,692 studies plus an 8 additional from hand searching. Duplicates, articles that did not meet the search criteria, and studies that did not include a qualitative synthesis were excluded which yielded 19 studies. Three reviewers were utilized, with two reviewing the articles for quality and the third was utilized to settle disputes. Of the 19 studies, the study design of 8 articles were randomized controlled trials (RCT), 1 article was a prospective longitudinal quasi-experimental study, 3 articles were case series, and the final 7 articles were case reports. Two independent reviewers evaluated the RCT studies and the prospective longitudinal quasi-experimental study for bias. Of these 9 studies, two studies met the Downs and Black rating of ‘‘excellent,’’ and the remaining 7 met the rating of ‘‘good”.10 SUMMARY OF INTERVENTION Parameters of BFRT used in each study varied slightly based on application and musculoskeletal system disorder. In the RCTs and case reports, the frequency of BFRT ranged from 1 to 6 sessions per week and 1 to 4 times per week, respectively. The intensity during the RCTs was 20-30% of the subjects calculated 1 repetition maximum (1RM). In the case-control designs, intensity was based on 15RM, 25RM, 20% 1RM, and 30% 1RM. For RCTs, the intervention lasted between 1 and 16 weeks while for case control studies it lasted between 1 and 12 weeks. For RCTs and case-control studies, intervention sessions varied from 1 to 5 sets of 15 to 30 repetitions or until failure. Rest intervals ranged from 30 seconds to 1 minute between sets. There was 1 case control study that reported no rest and 2 reported occlusion for 30 minutes to 1 hour. The BFRT devices included Sports Rehab Tourniquet®, Delphi PTS ii portable tourniquet system®, KAATSU master®, Hokanson AG101 cc17 thigh cuff™, 180 x 80 mm cuff size, 150 mm cuff size, 34-inch tourniquet, and knee wraps.10 Parameters for the BFRT device for the RCTs ranged from 160-200 mmHG or 70% to 80% occlusion. However, the case series and case report designs varied between 100-110 mmHG or 50% to 80% occlusion. Exercise selection in the RCTs included leg press, leg extensions, reverse press, or a combination of the exercises. In the case series and case reports, exercise selection included leg press, knee extensions, reverse leg press, squats, half squats, leg curls, resisted ankle eversion, seated, and standing calf raises, and Romanian deadlifts. However, exercise progression was not mentioned in all studies. In the RCTs, training load, final exercise occlusion pressure, and volume were altered. In the case series and case reports, load was altered so that the patient could not perform >15 repetitions, increased 10% if patient could perform 1 set in >2 minutes, and increased by 5 kg if the patient could perform >15 repetitions in the second set. SUMMARY OF OUTCOMES To examine the safety of BFRT, the authors for the guiding systematic review divided the results of the studies based on the reported events. Reported events were defined here as what adverse effects occurred during treatment if any. The data were categorized into one of 3 categories: no adverse events, common adverse events, and rare adverse events. No adverse events were defined as a study that reported no adverse effects from the intervention.11 Common adverse events were defined as effects that were no more than moderate severity, short term, had no impact on the patient’s function, all effects are transient or reversible, and there was no alteration to therapy needed due to the short term nature of the effects. Rare adverse events were defined as being severe, long term, distressing to the subject, and/or those that required further treatment to correct.12 To separate the data, the authors used a modified scale that included qualitative descriptions as well as incidence rates for each event. The modified scale was based off previous literature that investigated adverse effects for other therapeutic interventions.13 Specifically related to BFRT no adverse events were defined, as having had no harmful effects and the patient was able to complete the intervention as prescribed. Common adverse effects were defined as temporary muscle soreness, acute Safety of Blood Flow Restriction Training for Musculoskeletal Disorders: An Evidence-to-Practice Review 14 Copyright © by Indiana State University Clinical Practice in Athletic Training All rights reserved. ISSN Online 2577-8188 Volume 5 – Issue 2 – September 2022 muscle pain, acute fatigue, intolerance to intervention, slight discomfort, or dull pain. Rare adverse events were those that had an incidence rate between 1 and 10 in 10,000 cases as well as those where a serious medical condition occurred.10 FINDINGS AND CLINICAL IMPLICATIONS The guiding systematic review identified that BFRT was a safe intervention for adult patients based on predetermined safety recommendations.10,14 Table 1 provides the recommended safety guidelines. These recommendations specified cuff application, cuff type, occlusion pressure, exercise stimulus, type, and load, training volume, rest time, and training frequency.14,15 A RCT performed by Tennent et al. on postoperative non-reconstructive knee arthroscopy patients utilized single and multi-joint leg exercises at 30% of the subjects one rep max (1RM) at 80% limb occlusion pressure.16 These subjects completed 4 sets of 30, 15, 15, 15 reps separated by 1 minute of rest in between sets twice a week for six weeks.16 This study followed all 9 safety guidelines outlined below and no adverse events were reported.16 Similarly, a RCT performed by Ferraz et al. studied patients with knee osteoarthritis followed similar protocols to the previous RCT, followed all 9 of the safety guidelines, and also found no adverse effects.17 Another RCT performed by Hughes et al. compared BFRT with light exercise to high intensity resisted exercise alone on participants following ACL reconstruction and a non-injured control.8 They followed 8 of the 9 recommended guidelines for BFRT as described in this review and had no adverse reactions.8,10 Six RCT and four case series found no adverse effects from BFRT.10 Eight of these studies followed 7 or more of the 9 guidelines. The studies performed by Bryk et al. and Gaunder et al. following 6 and 5 respectively.18,19 Participants in a total of 6 studies, 3 RCTs and 3 case studies, had common adverse effects. The RCT conducted by Ohta et al. in 2003 compared the use of BFRT with exercise to the same exercises without BFRT for participants with ACL reconstruction but only followed 6 of the 9 recommendations.20 Discomfort and dull pain in the limb after 12 minutes of occlusion caused two participants to withdraw from the study. Table 1. BFRT Recommended Guidelinesa Type Guidelines Cuff application Around the limb proximal to the muscle(s) being trained Cuff type Wider for the leg (6-13.5 cm) and narrower for the arm (3-6 cm) Occlusion Pressure Upper Extremity: 40% to 50% of limb occlusion pressureb Lower Extremity: 50% to 80% of limb occlusion pressurea,b Exercise stimulus Aerobic: minor increase or maintenance of muscle mass and strength Low-load resistance: substantial increase in muscle mass and strength Type of exercise Single- and multi-joint exercises are beneficial Exercise loads ~20-40% 1 rep max Training volume 50-80 repetitions/exercise Rest time 30-45 seconds; maintain occlusion Training frequency 2-4 sessions/week with the addition of high-load resistance without BFRT for more active patients Abbreviation: BFRT = Blood flow restriction training aGuidelines adapted from Scott, Loenneke, Slattery, and Dascombe (2015).14 bGuideline adapted from Patterson, Hughes, Warmington, et al. (2019).15 Safety of Blood Flow Restriction Training for Musculoskeletal Disorders: An Evidence-to-Practice Review 15 Copyright © by Indiana State University Clinical Practice in Athletic Training All rights reserved. ISSN Online 2577-8188 Volume 5 – Issue 2 – September 2022 They used a single pressure of 180 mmHg for all patients.20 Likewise two studies, one with male subjects and one with female subjects, performed by Segal et al. examined the use of BFRT in patients with knee osteoarthritis. These studies used the same parameters outlined above by Tennent et al., however these studies used a standard 160-200 mmHG for all participants instead of a percentage of the individuals total limb occlusion pressure.21,22 Each study had a single participant drop out due to inability to tolerate BFRT, but no other participants exhibited any adverse effect.21,22 Utilizing a single pressure does not fall within the recommended guidelines of 50%-80% occlusion pressure.10 The pressure applied to the limb must be calculated for each patient. Five of these studies followed 7 or more of the 9 guidelines, with the final study following 6 guidelines. The final three case reports experienced rare adverse events. In two of the three cases with adverse events, it was stated that the individual had a preexisting condition. A case report by Noto et al. saw a patient develop Paget-Schroetter Syndrome when only 1 out of the 9 guidelines was followed.23 However, the authors noted that this patient had a history of localized edema in the left clavicle.10 The lack of guidelines followed, including occlusion of the upper extremity for long durations of 30 minutes to 1 hour, and preexisting condition are both factors that lead to the patient’s development of Paget-Schroetter Syndrome.10,23 A case report by Iverson et al. of a patient knee articular cartilage resection and microfracture and a case report by Krieger et al. of a patient with an ankle sprain, reported that the patient developed rhabdomyolysis after just a singular treatment.24,25 In both cases, the authors concluded that this was a freak occurrence and both subjects made a full recovery and were able to continue BFRT training.24,25 Additionally, the subject of the case report by Iversen et al. had a history of deep vein thrombosis after knee surgery.10,24 Once this subject had been treated and recovered from rhabdomyolysis, they were able to return to the study and complete BFRT without any further complications. In the case by Krieger et al., the subject did not have any known preexisting conditions, but it should be noted that the exercise load is not specified.25 Preexisting conditions should not be seen as an absolute contraindication for BFRT use and individuals with preexisting conditions are still able to experience the benefits of BFRT. To limit adverse events, future research should explore in depth safety precautions and guidelines, specifically for at-risk populations with specific factors or indicators, while continuing to explore mechanisms to improve clinician and patient adherence to the guidelines already outlined.10 This available research indicates that there is no greater risk for patients who use properly implemented BFRT than those who only use traditional therapeutic techniques. It is suggested that if the 9 guidelines are followed, the worst adverse effect that a patient would experience is mild discomfort and transient muscle pain. However, the use of BFRT is not completely devoid of risk and therefore only healthcare practitioners who wish to implement BFRT into their rehabilitation should be properly trained on the parameters and safety guidelines.10 CLINICAL BOTTOM LINE Blood flow restriction therapy has been found to have little to no adverse effects on patients with knee related musculoskeletal disorders.10 The risk of adverse effects is minimal when the 9 safety guidelines are followed as well as ensuring that the patient does not have a history of vascular disorders such as deep vein thrombosis.10 In particular, BFRT can be particularly useful in rehabilitation of post-operative ACL reconstruction. Hughes and colleagues found that although muscle pain was higher for both the ACL reconstruction BFRT and the non-injured BFRT groups, knee pain was less than that of the ACL reconstruction without BFRT.8 As discussed, BFRT can be a useful therapeutic intervention; however, certain parameters Safety of Blood Flow Restriction Training for Musculoskeletal Disorders: An Evidence-to-Practice Review 16 Copyright © by Indiana State University Clinical Practice in Athletic Training All rights reserved. ISSN Online 2577-8188 Volume 5 – Issue 2 – September 2022 should be followed during use. Most importantly, the athletic trainer must be trained by the accredited medical device manufacturer before using the BFRT device. The athletic trainer should choose the appropriately sized cuff for the patient to ensure that the BFRT device can function as intended. It is critical that cuff pressure be individualized to each patient as well as using cuffs that disperse the occlusion pressure around the circumference of the given extremity for not only safe, but effective implementation of BFRT. In addition to cuff size and cuff type, the guidelines of cuff application, limb occlusion pressure, exercise stimulus, type of exercise, exercise loads, training volume, rest, and training frequency should be followed in order to ensure safe implementation of BFRT.10 Further research is needed to make definitive conclusions about the absolute safety in all patient populations and for other injuries such as upper extremities and low back pain. Based on the findings in the guiding systematic review, athletic trainers should use caution when considering the use of cuffs for postoperative patients. First, they should be required to take the recommended training offered by the manufacturing company in order to be trained in cuff selection and application for the BFRT device. Next, clinical guidelines should be created for BFRT cuff use for low-load use during rehabilitation so that the proper protocols are followed including but not limited to individualized cuff pressure. Finally, athletic trainers should record observations and results for patient outcome analysis related to the efficiency of BFRT on a case-to-case basis to inform future clinical decision making. REFERENCES 1. Serpell BG, Scarvell JM, Ball NB, Smith PN. Mechanisms and risk factors for noncontact ACL injury in age mature athletes who engage in field or court sports: A summary of the literature since 1980. J Strength Cond Res. 2012;26(11):3160-3176. https://doi.org/10.1519/JSC.0b013e318243fb5a. 2. Renstrom P, Ljungqvist A, Arendt E, et al. Non-contact ACL injuries in female athletes: An International Olympic Committee current concepts statement. Br J Sports Med. 2008;42(6):394-412. https://doi.org/10.1136/bjsm.2008.048934. 3. Anderson MJ, Browning WM, 3rd, Urband CE, Kluczynski MA, Bisson LJ. A systematic summary of systematic reviews on the topic of the anterior cruciate ligament. Orthop J Sports Med. 2016;4(3):2325967116634074. https://doi.org/10.1177/2325967116634074. 4. Hewett TE, Ford KR, Hoogenboom BJ, Myer GD. Understanding and preventing ACL injuries: Current biomechanical and epidemiologic considerations - update 2010. N Am J Sports Phys Ther. 2010;5(4):234-251. 5. Paterno MV, Ford KR, Myer GD, Heyl R, Hewett TE. Limb asymmetries in landing and jumping 2 years following anterior cruciate ligament reconstruction. Clin J Sport Med. 2007;17(4):258-262. https://doi.org/10.1097/JSM.0b013e31804c77ea. 6. Mason MJS, Owens JG, Brown LWJ. Blood flow restriction training: Current and future applications for the rehabilitation of musculoskeletal injuries. Tech Orthop. 2018;33(2):71. https://doi.org/10.1097/bto.0000000000000301. 7. Hughes L, Rosenblatt B, Paton B, Patterson SD. Blood flow restriction training in rehabilitation following anterior cruciate ligament reconstructive surgery: A review. Tech Orthop. 2018;33(2):106-113. https://doi.org/10.1097/BTO.0000000000000265. 8. Hughes L, Paton B, Haddad F, Rosenblatt B, Gissane C, Patterson SD. Comparison of the acute perceptual and blood pressure response to heavy load and light load blood flow restriction resistance exercise in anterior cruciate ligament reconstruction patients and non-injured populations. Phys Ther Sport. 2018;33:54-61. https://doi/org/10.1016/j.ptsp.2018.07.002. 9. Nakajima T, Kurano M, Iida H, et al. Use and safety of KAATSU training: results of a national survey. Int J KAATSU Train Res. 2006;2(1):5-13. https://doi.org/10.3806/ijktr.2.5. https://doi.org/10.1519/JSC.0b013e318243fb5a https://doi.org/10.1136/bjsm.2008.048934 https://doi.org/10.1177/2325967116634074 https://doi.org/10.1097/JSM.0b013e31804c77ea https://doi.org/10.1097/bto.0000000000000301 https://doi.org/10.1097/BTO.0000000000000265 https://doi/org/10.1016/j.ptsp.2018.07.002 https://doi.org/10.3806/ijktr.2.5 Safety of Blood Flow Restriction Training for Musculoskeletal Disorders: An Evidence-to-Practice Review 17 Copyright © by Indiana State University Clinical Practice in Athletic Training All rights reserved. ISSN Online 2577-8188 Volume 5 – Issue 2 – September 2022 10. Minniti MC, Statkevich AP, Kelly RL, et al. The safety of blood flow restriction training as a therapeutic intervention for patients with musculoskeletal disorders: A systematic review. Am J Sports Med. 2020;48(7):1773-1785. https://doi.org/10.1177/0363546519882652. 11. White A, Hayhoe S, Ernst E. Survey of adverse events following acupuncture. Acupunct Med. 1997;15(2):67-70. https://doi.org/10.1136/aim.15.2.67. 12. Carnes D, Mullinger B, Underwood M. Defining adverse events in manual therapies: A modified Delphi consensus study. Man Ther. 2010;15(1):2-6. https://doi.org/10.1016/j.math.2009.02.003. 13. Brady S, McEvoy J, Dommerholt J, Doody C. Adverse events following trigger point dry needling: A prospective survey of chartered physiotherapists. J Man Manip Ther. 2014;22(3):134-140. https://doi.org/10.1179/2042618613y.0000000044. 14. Scott BR, Loenneke JP, Slattery KM, Dascombe BJ. Exercise with blood flow restriction: An updated evidence-based approach for enhanced muscular development. Sports Med. 2015;45(3):313-325. https://doi.org/10.1007/s40279-014-0288-1. 15. Patterson SD, Hughes L, Warmington S, et al. Blood Flow Restriction Exercise: Considerations of Methodology, Application, and Safety. Front Physiol. 2019;10:533. https://doi.org/10.3389/fphys.2019.00533. 16. Tennent DJ, Burns TC, Johnson AE, Owens JG, Hylden CM. Blood flow restriction training for postoperative lower-extremity weakness: A report of three cases. Curr Sports Med Rep. 2018;17(4):119-122. https://doi.org/10.1249/jsr.0000000000000470. 17. Ferraz RB, Gualano B, Rodrigues R, et al. Benefits of resistance training with blood flow restriction in knee osteoarthritis. Med Sci Sports Exerc. 2018;50(5):897-905. https://doi.org/10.1249/mss.0000000000001530. 18. Bryk FF, Dos Reis AC, Fingerhut D, et al. Exercises with partial vascular occlusion in patients with knee osteoarthritis: A randomized clinical trial. Knee Surg Sports Traumatol Arthrosc. 2016;24(5):1580- 1586. https://doi.org/10.1007/s00167-016-4064-7. 19. Gaunder CL, Hawkinson MP, Tennent DJ, Tubb CC. Occlusion training: Pilot study for postoperative lower extremity rehabilitation following primary total knee arthroplasty. US Army Med Dep J. 2017(2- 17):39-43. 20. Ohta H, Kurosawa H, Ikeda H, Iwase Y, Satou N, Nakamura S. Low-load resistance muscular training with moderate restriction of blood flow after anterior cruciate ligament reconstruction. Acta Orthop Scand. 2003;74(1):62-68. https://doi.org/10.1080/00016470310013680. 21. Segal N, Davis MD, Mikesky AE. Efficacy of blood flow-restricted low-load resistance training for quadriceps strengthening in men at risk of symptomatic knee osteoarthritis. Geriatr Orthop Surg Rehabil. 2015;6(3):160-167. https://doi.org/10.1177/2151458515583088. 22. Segal NA, Williams GN, Davis MC, Wallace RB, Mikesky AE. Efficacy of blood flow-restricted, low- load resistance training in women with risk factors for symptomatic knee osteoarthritis. PM R. 2015;7(4):376-384. https://doi.org/10.1016/j.pmrj.2014.09.014. 23. Noto T, Hashimoto G, Takagi T, et al. Paget-Schroetter syndrome resulting from thoracic outlet syndrome and KAATSU training. Intern Med. 2017;56(19):2595-2601. https://doi.org/10.2169/internalmedicine.7937-16. 24. Iversen E, Røstad V. Low-load ischemic exercise-induced rhabdomyolysis. Clin J Sport Med. 2010;20(3):218-219. https://doi.org/10.1097/JSM.0b013e3181df8d10. 25. Krieger J, Sims D, Wolterstorff C. A case of rhabdomyolysis caused by blood flow-restricted resistance training. J Spec Oper Med. 2018;18(2):16-17. https://doi.org/10.55460/1yxc-izh1. https://doi.org/10.1177/0363546519882652 https://doi.org/10.1136/aim.15.2.67 https://doi.org/10.1016/j.math.2009.02.003 https://doi.org/10.1179/2042618613y.0000000044 https://doi.org/10.1007/s40279-014-0288-1 https://doi.org/10.3389/fphys.2019.00533 https://doi.org/10.1249/jsr.0000000000000470 https://doi.org/10.1249/mss.0000000000001530 https://doi.org/10.1007/s00167-016-4064-7 https://doi.org/10.1080/00016470310013680 https://doi.org/10.1177/2151458515583088 https://doi.org/10.1016/j.pmrj.2014.09.014 https://doi.org/10.2169/internalmedicine.7937-16 https://doi.org/10.1097/JSM.0b013e3181df8d10 https://doi.org/10.55460/1yxc-izh1 ABSTRACT