Welcome to the 5th edition of the Learn.Physio Research Review!

Happy New Year everyone and welcome to Issue 5 of my Research Reviews!

I hope you have all had an enjoyable festive season and that you’ve started 2021 happy, safe and well!

In this issue I am going to dive into 2 recent papers on a topic that I get asked my opinion about on a regular basis – Blood Flow Restriction (BFR) training in the ACLR patient.

I really enjoyed delving a bit deeper into the BFR world, and it was really interesting to see that 2 papers had differing conclusions about the benefits of BFR in ACLR patients – and its certainly changed my views on it. It’s a slightly longer read than my previous Research Reviews, but I felt like I needed to be more thorough in my appraisal to highlight the differences between the 2 papers to help you guide your clinical practice.

I hope you enjoy my latest issue of Research Reviews and I look forward to sharing with you plenty more Research Reviews over the course of 2021!

Introduction

ACL reconstruction (ACLR) is a very common orthopaedic procedure worldwide, and is often the treatment option for many following ACL injury (despite strong evidence suggesting non-operative management is a very good alternative; but this discussion is for another time and place).

Following the injury itself, and subsequent surgery, a significant quadriceps strength loss is often seen, and can still be persistent many years after the ACLR. This persistent quadricep strength loss is problematic in many ways and can impact on both short-term outcomes (altered walking and running biomechanics) and long-term outcomes (increased risk of recurrent knee injuries, decreased quality of life and function, and post-traumatic osteoarthritis).

Restoring quadriceps strength to >90% limb symmetry index has been shown to result in better short term and long-term outcomes, however some patients still struggle to achieve this target despite their dedication and persistence to ACLR rehab.

Blood flow restriction (BFR) has been studied and identified as a novel solution to help those with persistent quadriceps weakness following ACLR. If you’re unfamiliar with BFR, a tourniquet or pressure cuff, is applied to the upper thigh to compress the underlying vascular structures during exercise. By compressing the vascular structures, it allows blood from the arteries into the limb (oxygenated blood flowing from the heart) but restricts the blood returning from its journey around the lower limb (venous blood or de-oxygenated blood).

By restricting the blood flow, it allows patients to fatigue in their muscles much quicker and at much lighter loads.

The biological and physiological mechanisms behind this blood flow restriction are thought to stimulate muscle growth and strength by;

• Metabolic accumulation that encourages increases in anabolic growth factors
• Enhanced fast twitch muscle fibre recruitment
• Increased protein synthesis through the rapamycin (mTOR) pathway
• Decreases in myostatin expression

The quadriceps strength loss following ACLR are associated with decreased fast-twitch fibre recruitment and frequency, and increased myostatin expression – so in theory, by being able to train to muscular fatigue with much lower intensity and loads, yet still get the same strength and hypertrophy gains, it makes sense to consider BFR in ACLR rehab protocols.

The purpose of this study was to incorporate BFR alongside high-intensity concentric or eccentric exercise into ACLR rehab and examine its effects on the recovery of quadriceps strength, activation and atrophy.

The authors hypothesised that BFR would have greater quadriceps strength and activation, as well as less muscle atrophy, than patients not receiving BFR.

Methods

48 patients aged between 14yrs and 30yrs who were scheduled to undergo primary ACLR were randomly assigned into 1 of 4 intervention groups:

• Concentric exercise only
  • 5 sets of 10 reps with 2min rest between sets
  • Concentric phase set at 70% of 1RM
  • Eccentric phase set at 20% 1RM
• Eccentric exercise only
  • 5 sets of 10 reps with 2min rest between sets
  • Eccentric phase set at 70% 1RM
  • Concentric phase set at 20% 1RM
• Concentric exercise + BFR (80% of full-limb occlusion pressure)
  • Same protocol as concentric exercise only
• Eccentric exercise + BFR (80% of full-limb occlusion pressure)
  • Same protocol as eccentric exercise only

NB: BFR unit was PTS personalised tourniquet system (Delfi Medical Innovations). Cuffs were deflated at the completion of each set and remained deflated for the 2min rest period before being re-inflated just prior to the next set.

The above interventions were delivered 2x per week for 8 weeks on a specially designed leg press system call BLAST! (Bio Logic Engineering) that can be adjusted for the concentric and eccentric loads (beginning at 10 weeks post-op).

Prior to the commencement of the interventions, all participants underwent a standard ACLR rehab protocol focusing on the following:

• First 4 weeks was focused on reducing pain/swelling, restoring full ROM, improving quadriceps muscle activation and achieving full weight bearing whilst walking.
• From week 4 through to week 16 the protocol focused on increasing strength of the quads, hamstrings and hip muscles, as well as improving balance.
• NOTE: remember that the BFR was only used for Leg Press exercise, not others such as knee extensions, squats, step ups etc.
• After week 16, but not before they could do 15x reps of a single-leg leg press at their body weight, they could then commence running straight lines.
• Progress to pre-injury activity was then gradually progressed thereafter

Outcome measures were obtained at 4 time points:

• Pre-op (within 2 weeks of ACLR)
• Pre-intervention (before starting either one of the 4 interventions)
• Post-intervention (within 2 weeks after completing one of the 4 interventions)
• Return to activity (after they had been cleared to return to activity by their treating physician)

The primary outcomes being assessed were:

• Change in isometric and isokinetic quadriceps strength from pre-op to post-intervention
• Change in isometric and isokinetic quadriceps strength from pre-op to return to activity.

Secondary outcomes being assessed included; changes in IKDC scores over different time points, rectus femoris muscle volume and its central activation ratio (CAR), and changes in 1RM leg press strength.

Potential candidates were excluded if they had:

• Previous knee surgery
• Previous ACL injury
• Cardiac pacemaker
• History of DVT
• History of cerebrovascular disease
• Been using estrogen or progestin contraceptives
• History of sickle cell anaemia
• History of diabetes
• History of severe hypertension
• Any potential female who was pregnant, or planning to become pregnant over the next year

After ACLR was performed, and over the course of the study, 14 patients ceased participation or dropped out of the study. This left 34 participants (19 females, 15 males, average age 16.5yrs) randomly assigned across the 4 intervention groups available for data analysis.

Results

Primary outcome analysis:

• No significant between group differences in the change from pre-op to post intervention for maximal isokinetic knee extension, maximal isometric knee extension, rectus femoris muscle volume and CAR
• No significant between group differences in the changes from pre-op to return to activity for the same outcomes mentioned above.

Secondary outcome analysis:

• No between group differences were observed for any of the other secondary outcome measures observed such as the change in IKDC over time, 1RM leg press and rectus femoris muscle volume.

In a post-hoc analysis, due to the lack of differences between the 4 intervention groups, the authors decided to collapse the 4 groups into 2;

• Those that were randomised to receive BFR (concentric + BFR and eccentric + BFR) (n=18)
• Those who did not receive BFR (concentric only and eccentric only) (n=16).

When looking at the results in this fashion, the authors still found no significant differences between groups for any of the primary or secondary outcome measures at any given time points.

Discussion

These findings were very interesting, considering work that has been previously performed in the BFR space that has showed increased muscle mass and volume in health participants, and BFR work that has been done specifically on ACLR populations (one of which I will review in article 2).

Part of the reason that this trial is showing different results to others may be due to the fact that there are differences in the BFR protocols delivered in each study; most notably the occlusion pressure and the amount of BFR treatment sessions per week

Curran and colleagues noted that their protocol used 80% limb occlusion (ranging from 110-186 mm Hg), whereas others have used pre-determined occlusive pressures (180 mm Hg or 180-260 mm Hg), which is comparatively higher than this study (Ohta et al 2003 and Takarada et al 2000).

It would be fair to say then that to get a therapeutic effect from BFR that pressures higher than 80% of an ACLR patient’s limb occlusion is necessary; however, Curran et al noted that the occlusion pressures they used were identical to those that led to improvements in quads strength and thigh girth in patients after arthroscopic knee surgery (Tennent et al 2017). Furthermore, higher occlusion pressures only seemed to have an effect on strength and hypertrophy when resistance training was completed at very low intensities or 20% 1RM (Lixandrao et al 2015).

In respect to frequency per week, Curran et al performed BFR 2x per week with some others reporting the use of low-intensity BFR up to 5x per week (Loenneke et al 2011).

So, it seems from this research article that when the ACLR person can tolerate high-intensity loads (at least 70% 1RM), the addition of BFR is not worthwhile. However, when the person can not tolerate heavy loads (ie. the first 4-8 weeks following ACLR), the addition of BFR may mitigate strength and muscle volume loss.

Let’s look at that scenario in another paper on BFR in an ACLR population.

Introduction

The primary goal of ACLR rehab is to return the patient to their pre-injury level of status with a low risk of re-injury. Heavy-load resistance training using external loads of at least 60% of an individual’s 1 repetition maximum (1RM) are recommended to stimulate skeletal muscle hypertrophy and strength adaptations. However, these heavy loads may be not tolerated +/- contraindicated in ACLR patients early in their rehab depending on associated injuries or procedures such as bone bruising or meniscus repairs.

Prior to the completion of this work by Hughes and colleagues, BFR had not been directly compared to heavy-load resistance training (HLRT), so they aimed to compare the effectiveness of BFR and HLRT for improving skeletal muscle hypertrophy, strength, physical function, pain and effusion in ACLR patients during rehabilitation.

Methods

28 patients scheduled for unilateral ACLR (mix of hamstring and BPTB autografts) were recruited for this study. All participants were active, non-smokers, had no known history of central or peripheral neurological impairment and were free of any cardiac, pulmonary or metabolic conditions.

Exclusion criteria included:

• Multiple ligament ruptures
• Rheumatoid arthritis
• History of DVT or vascular pathology in any lower limb
• Intra-articular injections into the knee in the preceding 6 months
• Use of anticoagulant medications
• Inability to follow instructions during exercise
• Post-surgical leg bracing

Participants were randomised to either the BFR group (n=14) or the HLRT group (n=14).

They completed 4 testing sessions throughout the study where outcome measures were recorded:

1. Pre-surgery
2. Post-surgery (in the first week of the resistance training program)
3. Mid-training (week 4-5 of the resistance training program)
4. Post-training (within 1 week after completing the 8-week program)

The outcome measures were:

• 10RM unilateral strength via leg press
• Isokinetic quadriceps and hamstring strength
• Muscle morphology (muscle thickness, pennation angle and fascicle length of the vastus lateralis)
• IKDC
• KOOS
• Lower extremity function scale (LEFS)
• Lysholm knee-scoring scale (LKSS)
• Tegner activity scale
• Modified star excursion balance test
• ROM
• Effusion
• Knee joint laxity via KT-1000

The resistance training intervention for both groups was an 8-week, progressive overload program consisting only of a unilateral leg press that was carried out 2x per week under the supervision of a trained member of the research team. The difference being that the BFR group utilised a 30% 1RM load throughout the 8-week intervention period, and the HLRT group utilised at 70% 1RM load during the 8-week intervention period. Sets and reps are as follows:

• BFR: 4 sets (30 reps, 15 reps, 15 reps, 15 reps) at 30% 1RM: 30sec rest between sets
• HLRT: 3 sets of 10 reps at 70% 1RM: 30sec rest between sets

This commenced any time after week 2 post-op after the sutures had been removed, and surgeon approval granted. Each resistance training session was separated by at least 48hrs.

In addition to the supervised unilateral leg press resistance training intervention, all participants received a standardised rehabilitation program that was to be conducted at home independently 3x per week.

The BFR unit was an automatic personalised tourniquet system designed to automatically calculate limb occlusion pressure. This was set at 80% limb occlusion pressure to maximise fast twitch fibre recruitment and maximise muscle adaptations. This unit and set up is similar to that used in the Curran et al (2020) paper.

Results

Four participants were lost before completing the study, leaving 12 ACLR patients (mean age 29yrs of age) in each group. There were no significant differences between groups for any of the baseline anthropometric variables, exercise intervention adherence or training load changes and no adverse events were reported. The post-op testing session and first week of the strengthening intervention started on average between weeks 3-4 post-op for both groups.

In relation to the main outcome measures for 8 weeks of supervised leg press training, the following results were obtained:

• 10RM leg press strength – both groups experienced significant increased in 10RM strength in both limbs with no group differences
• Isokinetic strength
  • 60deg/sec knee extension: no significant differences between groups
  • 150deg/sec and 300deg/sec knee extension a significant loss of peak torque was observed in the HLRT group, but not the BFR group
  • Significant losses in peak knee flexion torque were observed at all speeds in the HLRT group, but not the BFR group.
• Muscle Morphology – Both groups experienced significant increases in muscle thickness and pennation angle over the 8 weeks of resistance training with no significant differences observed between the 2 groups. There were no changes in fascicle length over the intervention period.
• IKDC, LEFS, LKSS and KOOS – over 8 weeks of training, both groups improved but there were significantly greater increases in all self-reported measures for the BFR group
• Modified SEBT – Over 8 weeks of training, both groups improved, but there were significant greater increases in all reach distances in the BFR group
• Pain, effusion and ROM – over 8 weeks of training, both groups improved, but there was a significant greater improvement for these outcomes in favour of the BFR group
• Laxity – over the 8 weeks of training there were no significant differences between groups.

Discussion

The findings of Hughes and colleagues work is very interesting, and in contrast to the findings of Curran et al (2020). The big takeaway for me from Hughes’ paper was that, although there was no difference between groups for increasing muscle strength and hypertrophy, there were improvements seen in favour of BFR for patient reported outcomes measures and reduced pain and knee effusion; with the last 2 points (pain and effusion) often being a major hurdle to rehab progressions throughout the first 8-12 weeks following ACLR.

The different conclusions drawn from each paper are what can make life as a busy clinician very hard at times. Here we have 2 very similarly designed papers. Both had similar inclusion/exclusion criteria. Both had a 2x per week unilateral leg press intervention period for 8 weeks. Both used a similar BFR protocol. To be fair, they did have slightly different outcome measures, but Curran et al report that the addition of BFR was not superior to HLRT-alone (either concentric or eccentric contractions) in regards to quadriceps strength and hypertrophy in a population of ACLR patients, and then Hughes et al report that the addition of BFR is beneficial particularly when it comes to pain and effusion in the ACLR patient.

As a result, I think it’s very important to understand the key differences between the study designs of each research paper presented today – and for me there were three standouts.

Firstly, the work by Curran et al was on a group of ACLR patients who were approximately 10 weeks post-op ACLR, who for what one can assume, were doing reasonably well for the first 10 weeks with their rehab plan without BFR. This is in contrast to Hughes et al who had patients commence the intervention from around week 3 post-op. Would we see non-significant results in Curran et al’s trial if it was commenced around weeks 3-4 with the heavy 70% loads?

Secondly, the age of the participants in Curran et al were much younger than those in Hughes et al (mean 16.5yrs vs 29yrs). Does age have an effect on outcomes, particularly when it comes strength, muscle hypertrophy and pain tolerance? Would we still see the non-significant results in Curran’s and colleague’s trial if we had an older population of ACLR patients?

Lastly, as mentioned just above, other big difference between the two trials was the Curran used BFR during both concentric and eccentric groups with 70% 1RM loads (with their clinical reasoning for 70% 1RM loads previously mentioned), whereas Hughes et al utilised BFR with 30% 1RM loads.

Summary

BFR has been around for quite some time now and it’s nice to have it applied to specific populations such as ACLR patients.

Based on the current BFR and ACLR literature, once the person has been screened appropriately for underlying medical and vascular conditions, it does appear to be safe and effective (when performed under supervision) in a population of ACLR patients from week 3 post-op, but does not appear to be beneficial when added to strengthening programs when patients can already tolerate heavy loads of 70% 1RM or above.

I must admit, prior to reviewing these 2 papers in more detail, I had reservations of using BFR in my ACLR patients, and to this very day, I have never used BFR with any of my patients, for the main reason being I was concerned about safety, especially the risk of DVT and neurovascular compromise. The findings from both of these papers show that when screened appropriately, and when performed under supervision, that these concerns of mine can be allayed.

I also questioned in the past, and to be honest, I still question that, if we get the loading right early with appropriate exercise (including allowing the patient to perform open chain exercises in the first 4-6 weeks (in the appropriate ROM, frequency, load and intensity) that we can also improve pain, effusion and strength outcome measures without BFR. Just like those patients who were seemingly doing quite well in Curran and colleague’s trial.

For me personally, I don’t like to make my patients reliant on me, and I want to empower my patients to drive their own recovery and get the work done themselves – and I feel that this is an important part of my job. To have to get the person to come in 2x per week for 8 weeks and supervise them with the use of a BFR unit on a leg press machine; I’m not sure is the best use of my patient’s time and money. Especially if they can achieve good results doing the basics well at home, or in the gym, independently.

Of course, we could use BFR in other quad dominant exercises such as squats, lunges, knee extensions, step ups/downs etc to maximise “bang for buck” for the patient in supervised rehab sessions, but we also need to tread very carefully when we generalise these findings from Curran and Hughes to other exercises in a rehab program that have not been looked at previously – especially when we’re looking at it from a safety point of view, and whether or not we are compromising the vascular system with repeated occlusions with multiple exercises in a session.

So, will I personally change my current management of ACLR patients? Not at this stage no, but I will certainly add it to my physio tool-kit from now on, and be much more comfortable in using BFR in the future with any patients who may be really struggling to get their pain and effusion under control in the first 10-12 weeks following their ACLR.

If you’re looking to go down a rabbit-hole of BFR information, I strongly urge you to read the paper by Patterson et al (2019). You will find a link to the full text paper by clicking on the link in the reference section below.

References:

Article 1

Curran MT, Bedi A, Mendias CL, Wojtys EM, Kujawa MV, Palmieri-Smith RM. Blood Flow Restriction Training Applied With High-Intensity Exercise Does Not Improve Quadriceps Muscle Function After Anterior Cruciate Ligament Reconstruction: A Randomized Controlled Trial. Am J Sports Med. 2020 Mar;48(4):825-837. doi: 10.1177/0363546520904008. PMID: 32167837.

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 Feb;74(1):62-8. doi: 10.1080/00016470310013680. PMID: 12635796.

Takarada Y, Takazawa H, Ishii N. Applications of vascular occlusion diminish disuse atrophy of knee extensor muscles. Med Sci Sports Exerc. 2000 Dec;32(12):2035-9. doi: 10.1097/00005768-200012000-00011. PMID: 11128848.

Tennent DJ, Hylden CM, Johnson AE, Burns TC, Wilken JM, Owens JG. Blood Flow Restriction Training After Knee Arthroscopy: A Randomized Controlled Pilot Study. Clin J Sport Med. 2017 May;27(3):245-252. doi: 10.1097/JSM.0000000000000377. PMID: 27749358.

Lixandrão ME, Ugrinowitsch C, Laurentino G, Libardi CA, Aihara AY, Cardoso FN, Tricoli V, Roschel H. Effects of exercise intensity and occlusion pressure after 12 weeks of resistance training with blood-flow restriction. Eur J Appl Physiol. 2015 Dec;115(12):2471-80. doi: 10.1007/s00421-015-3253-2. Epub 2015 Sep 1. PMID: 26323350.

Loenneke JP, Wilson JM, Marín PJ, Zourdos MC, Bemben MG. Low intensity blood flow restriction training: a meta-analysis. Eur J Appl Physiol. 2012 May;112(5):1849-59. doi: 10.1007/s00421-011-2167-x. Epub 2011 Sep 16. PMID: 21922259.

Article 2

Hughes L, Rosenblatt B, Haddad F, Gissane C, McCarthy D, Clarke T, Ferris G, Dawes J, Paton B, Patterson SD. Comparing the Effectiveness of Blood Flow Restriction and Traditional Heavy Load Resistance Training in the Post-Surgery Rehabilitation of Anterior Cruciate Ligament Reconstruction Patients: A UK National Health Service Randomised Controlled Trial. Sports Med. 2019 Nov;49(11):1787-1805. doi: 10.1007/s40279-019-01137-2. PMID: 31301034.

Patterson SD, Hughes L, Warmington S, Burr J, Scott BR, Owens J, Abe T, Nielsen JL, Libardi CA, Laurentino G, Neto GR, Brandner C, Martin-Hernandez J, Loenneke J. Blood Flow Restriction Exercise: Considerations of Methodology, Application, and Safety. Front Physiol. 2019 May 15;10:533. doi: 10.3389/fphys.2019.00533. Erratum in: Front Physiol. 2019 Oct 22;10:1332. PMID: 31156448; PMCID: PMC6530612.

Thanks for reading and staying up to date. I look forward to sharing more in the future.
 

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