Blood Flow Restriction Training and Uses in Rehabilitation

The strength of a muscle is the ability to produce a maximal force against an external resistance (Schoenfeld et al., 2021). Skeletal muscles must have enough strength to withstand the external resistance of gravity and our body weight to walk, stand up from a chair, or ascend and descend stairs. We must have enough strength to resist activities throughout our daily living, such as lifting a gallon of milk or pushing open a door. Outside the activities of daily living, our strength needs vary greatly and depend on our activity goals and lifestyle. A weightlifter will have different strength needs than an 80-year-old golfer.

Evidence shows that training load can influence muscular adaptations through metabolic, hormonal, neural adaptions, and cardiovascular responses to resistance training, and the magnitude of the load used (or the amount of weight lifted) is considered one of the most important training variables (Schoenfeld et al., 2021). A low repetition with heavy loads (1-5 repetitions per set with 80%-100% of a one repetition maximum (1RM) has been shown to optimize strength increases (Shoenfeld et al., 2021). Low-intensity resistance training is much less effective in increasing muscle strength and growth than moderate and high-intensity exercise, as outlined above. A real-world example would be as follows: a person can lift 100 pounds (lbs.) during a biceps curl but can only perform this once. 100 lbs. would be this person's 1RM for the biceps curl. According to the traditional model of resistance training for strengthening, this person would need to perform 1-5 repetitions per set at a training load of 80-100 lbs. to increase the strength of their biceps. In a clinical environment, it is difficult to establish a patient's 1RM, as many of our patients are injured or frail, or there is a lack of clinical equipment to establish this number. We modify strength training parameters by altering the amount of weight used and the number of reps and sets performed. Clinically, we tend to rely on manual muscle testing or dynamometry to establish the force produced by a given muscle. Still, some formulas can be used to predict this 1RM value, including bioelectrical impedance (Sue et al., 2022).

Hypertrophy is when the actual size of the muscle increases. Hypertrophy is optimized with moderate loads with 8-12 repetitions per set at 60%-80% of 1RM (Schoenfeld et al., 2021). Muscle hypertrophy is slow and virtually non-existent in the initial stages of resistance training, with most strength changes occurring from neural adaptations. However, within a few months of resistance training, hypertrophy becomes dominant due to increased myofibril and sarcomeres added in parallel and eventually increased diameter of individual fibers (Schoenfeld, 2010).

If a muscle is never challenged, it is never prompted to become stronger. If the stress on a muscle is confined to resistance well within its strength capabilities, it tells the muscle that it is as strong as it ever needs to be. Resistance is essential to increasing strength for any patient population. Through resistance training, a demand is placed on the muscle; there is neural recruitment of that muscle, the increased stress creates microscopic damage, and then the muscle repairs and recovers, increasing strength and size. Here, we will cover an overview of the physiology of muscle strengthening- this will not be a deep dive into the physiology, such as the Krebs and Cori Cycles, which play a significant role in how muscles are utilized but are outside this course's scope.

The physiology of muscle strength is a factor of five primary mechanisms: tensile strength, metabolic accumulation, muscle cell swelling, neural adaptations, and post-exercise hormones (Schoenfeld, 2010).

• Tensile stress: Development of strength and hypertrophy depends on progressive tensile loading and stretching of the muscle. This repetitive tensile stress creates micro-damage to the muscle fiber satellite cells. These cells increase in number, eventually fusing with existing cells to develop new myofibers.
• Metabolic Accumulation: This process is simultaneously facilitated by metabolites that stimulate pathways favoring muscle synthesis over degradation.
  • Lactic Acid- accumulation of lactic acid during exercise promotes muscle hypertrophy.
  • Creatine Kinase- an indicator of excessive muscle damage.
• Muscle Cell Swelling: During resistance training, intracellular swelling occurs, which is theorized to stretch the cell membranes, further stimulating metabolic signaling.
• Neural Adaptations: Not all muscle fibers are fired at once during exercise. This constant fluctuation of which myofibrils are stimulated allows for stronger contractions for longer (endurance). During resistance training, more muscle fibers are recruited to increase maximal power.
• Post-exercise Hormones: Insulin-like growth factor (IGF-1) and growth hormone (GH) are two of the main anabolic hormones in human muscle that have been shown to spike during resistance training and stimulate muscle growth.

There are, however, negative regulators of muscle growth. One significant factor is myostatin, which is crucial in inducing muscle atrophy (Jang et al., 2021). It has also been demonstrated that myostatin inhibition can protect against muscle atrophy and allow skeletal muscle to increase in size (Jang et al., 2021). When considering resistance training, minimizing or inhibiting the effects of myostatin would be desirable. Lactate that is released during exercise can inhibit myostatin.

These five factors will become important when discussing why BFR with low resistance training is highly effective and desirable when building muscle strength and hypertrophy in many patient populations.

Myostatin Inhibition

Until recent years, many of the potential benefits of BFR were thought to be limited to tissues undergoing occlusion distal to where the pressure is applied; however, recent findings indicate that there may be some benefit to tissues directly proximal to the occlusion site (Hedt et al., 2022). Increases in rotator cuff strength and limb circumference have been documented via electromyography (EMG) following BFR and low-intensity exercise (Hedt et al., 2022). It does appear, however, that there is a threshold of volume or cumulative time under occlusion for proximal effects to occur. Similar benefits have been demonstrated in the proximal strengthening of the gluteus maximus with occlusion training of the hip and lower extremity (Hedt et al., 2022). Unfortunately, the proximal effects spanning to other regions (chest muscles, back muscles, etc.) are highly understudied.

When providing patient interventions, the clinician must be aware of the safety, methods of safe implementation, clinical application, and efficacy. It is recommended that the clinician take appropriate training courses before utilizing BFR devices. Many courses are available, and depending on specific professional state practice, acts can be taken by licensed PTs, ATs, DCs, MDs, Doctors of Osteopathy (DOs), Nurse Practitioners (NPs), PAs, and (OTs). There are usually no prerequisites to these courses, which are available in person and online. Unfortunately, there is no certification process or process to ensure that a clinician completes any coursework before utilization with patients.

One of the most common questions about the safety of BFR revolves around clot formation or deep vein thrombosis (DVT). It is known that DVT is a risk of pneumatic tourniquet use during surgery. Most people are less aware that tissue ischemia after inflation stimulates the release of tissue plasminogen activator (TPA), which activates anti-thrombolytic proteins. When the tourniquet is deflated, this causes systematic thrombolysis in the affected limb (Kam et al., 2001). Studies investigating the potential of clot formation following the use of BFRT show no longstanding adverse effects following BFRT with low-resistance exercise. Some studies suggest a slight elevation of TPA following BFR exercise, suggesting a mild anti-thrombolytic effect (Nascimento et al., 2022). Nonetheless, there may be a potential for DVT formation in people with a complex medical history (Nascimento et al., 2022).

As with any other therapeutic intervention, especially in physical exercise and rehabilitation, safety considerations must be taken before beginning BFR with any patient. Regardless of age, when performing any resistance training or cardiovascular exercise, the patient must be medically well enough to participate in the exercise safely. If you are concerned about a patient's medical safety when exercising, then you should not consider the application of blood flow resistance to their rehabilitation. Again, as with any form of general exercise, consult with the referring physician if there is any doubt. In direct access states, however, there may not be a referring physician, so diligence is required when implementing any form of resistance or cardiovascular training. The clinician should consider whether BFRT has a clinically relevant benefit to the patient. Consideration should also be taken regarding other potential treatments or interventions that could provide similar results with less risk (Nascimento et al., 2022). Risk vs. benefit is a common consideration for any clinician, and this intervention should be no different.

Consider a patient's physical appearance before implementing BFR into your treatment plan. How is their circulatory system? Do they have poor capillary refill time, varicose veins, or indications of circulatory loss in their skin or nails? Do they have concerning health conditions in their medical history? Conditions such as uncontrolled hypertension, cardiopulmonary conditions, history of DVT, arterial calcification, diabetes, sickle cell trait, or active infection would serve as indications to take precautions when considering the use of BFRT. While there are no identified contraindications to the use of BFR, there are conditions that have been identified, and point values have been assigned that can serve as a screening to determine the appropriateness of implementation in a given patient. Given that no validated screening system has been developed, the following chart, adapted from Nascimento et al. (2022), can be a good start toward a patient safety screening system. Generally, a point value greater than five (5) should warrant not proceeding with BFR.

Additionally, the following flow chart can serve as an example of a decision tree to determine when to implement or exclude BFR into your training regime (AIS, n.d.).

BFR Decision Tree

First and foremost, the patient's needs must match the clinical benefits provided through BFRT. Once this has been confirmed, patient safety is the next most considerable determination before occlusion training. Based on current literature, including case reports, case studies, and randomized control trials, it has been determined that blood flow restriction provides a tremendous opportunity to accelerate rehabilitation and possibly aid in injury prevention safely. As with any other modality, BFR should be performed by professionals who have undergone appropriate training and education, but overall, it has been shown to be a safe and useful technique (Anderson et al., 2022).

There are many situations in which BFRT is utilized that do not follow evidence-based medical models. You can see these regularly used in gyms or by bodybuilders. Often, you will see people in these settings using narrow cuffs, other forms of straps, or non-pneumatic elastic bands, or where there is a single-size cuff that is cinched to the desired perceived tightness by the wearer. These are often used by lay people, who may not be fully aware of application parameters and can be ineffective or dangerous if utilized improperly. While this equipment is less expensive and easily attainable at sporting goods stores or online shopping sites, it should not be used in a medical setting.

Physical therapists and other medical professionals for whom BFR is within their scope of practice should use inflatable tourniquets that meet FDA standards. Pneumatic cuffs used for BFR fall under FDA Sec 878.5910, which defines a pneumatic tourniquet as "an air-powered device consisting of a pressure-regulating unit, connecting tube, and an inflatable cuff. The cuff is intended to be used to be wrapped around a patient's limb and inflated to reduce or totally occlude circulation" (U.S. Food and Drug Administration [FDA], 2023).

Pneumatic Cuff and Pump

Cuff placement for BFRT purposes should be as high proximally on the targeted limb as possible. For the upper extremity, this is between the axilla and the proximal biceps. The lower extremity is in the femoral crease, as proximal to the quadricep as possible; this allows for comfortable muscle contraction, protects superficial nerves, and allows for the lowest pressure required to create occlusion. If the cuff is placed over the thick portion of the muscle belly (quadriceps, for instance), it will take more pressure to push into the muscle before vascular occlusion will occur. The clinician should select a cuff size appropriate to the size of the involved limb, allowing for a small amount of overlap in the cuff ends to create even pressurization around the limb. If a cuff is too small and the ends do not wrap around sufficiently, the patient may experience pinching or discomfort, which may prevent them from participating in exercises. If a cuff is too large for the limb, it may not inflate adequately to provide a reliable reading of the inflation pressure.

The pressure required to create blood flow occlusion to a limb depends on many individual limb characteristics (Patterson et al., 2019). For maximal safety, reliability, and reproducibility, the pressure should be specific to the patient's limb (left or right), the cuff shape/width/length, and the application location. This is achieved by measuring the limb occlusion pressure (LOP) or the arterial occlusion pressure (AOP); both are accepted terminology. LOP is the minimal pressure to occlude arterial blood flow (Patterson et al., 2019). The gold standard for measuring LOP has been using a Doppler ultrasound technique to measure the exact pressure when arterial blood flow is disrupted. In the lower extremity, this can be measured at the dorsalis pedis or the posterior tibial artery. For the upper extremity, this is typically measured at the radial artery; this pressure is then utilized at varying percentages during BFRT to prevent mild hypoxia and ischemic effects but not to fully occlude arterial blood flow into the limb during rehabilitative exercises (McEwen et al., 2018). Because LOP has been shown to vary significantly between different people, it is suggested that clinicians measure LOP consistently for each patient (Evin et al., 2021). Recently, newer integrated models that automatically calculate LOP have emerged. The automatic pump versions have been shown to accurately measure LOP with no statistical difference from the previous gold standard of the Doppler technique (Abbas et al., 2022). It is generally recommended that pressures between 40-80% of the LOP be utilized during BFR training (Cognetti et al., 2022; Patterson et al., 2019). The cuff inflation should be limited to 40-50% of the LOP for the upper extremity and 60-80% of the LOP for the lower extremity (Smart Tools, n.d.). Exercise prescription depends on whether it is applied passively, with resistance training, or during aerobic exercise.

Doppler Ultrasound

In addition to improvements in cross-sectional area and overall muscle strength, recent studies have demonstrated improvement in the volume or amount of oxygen the body consumes (VO2 max) following BFRT (Bradley et al., 2023). Similarly, low to moderate-intensity aerobic training with BFR significantly improved overall aerobic capacity compared to aerobic exercise without BFR (Formiga et al., 2020). Interestingly, no significant improvement in aerobic capacity was noted with BFR combined with high-intensity aerobic exercise (Formiga et al., 2020). In 2022, Tan et al. (2022) studied the effects of BFR with low-intensity resistance training on microvascular rarefaction in the myocardium of hypertensive rats. He found that BFRT did improve the density and pressure of the microvascular vessels and improved microvascular circulation (Tan et al., 2022). These changes in the microvascular structure led to improved cardiac function and decreased blood pressure, achieving the preventative effect of early hypertension. While not conducted on human subjects, this is an exciting potential for disease prevention in humans, although further testing is warranted.

Resistance training is a well-known combatant of osteoporosis and a way to improve overall bone density. Studies involving low-intensity resistance training and BFR can increase osteoblastic activity to favor bone formation. Through BFR, this can be accomplished without placing the body under the physical stress of high-intensity resistance training. A meta-analysis conducted by Wang et al. (2023) reviewed 285 studies related to the effects of BFRT on bone metabolism. Ultimately, they included 12 studies in their review, which involved 378 participants. Their review indicated that BFR with low-intensity exercise demonstrated a better impact on bone health than that of low-intensity exercise alone but was less effective (minimally) than high-intensity training. Additionally, they discovered that walking with BFR had a better effect on bone health than without BFR. Wang et al. (2023) concluded that BFR with low-intensity exercise is an effective and efficient alternative to high-intensity training to promote gains in bone health for people who are not able to withstand the higher mechanical loads of high-intensity exercise. This may include "untrained individuals, older adults, or patients undergoing musculoskeletal rehabilitation" (Wang et al., 2023).

BFR has primarily been investigated for use in the treatment of orthopedic conditions. Some emerging studies investigate the outcomes of BFR in treating neurological conditions (Yuan et al., 2023).

BFRT is also being increasingly applied to the rehabilitation treatment of many chronic and systemic diseases. Rodrigues et al. (2020) conducted a study involving rheumatoid arthritis (RA). They deemed that pain experienced during exercise and the health assessment questionnaire scores were improved in the group participating in a 12-week training session with and without BFRT. The outcomes of this study showed that BFRT is a feasible treatment method for RA management. Another study found decreased insulin levels and sensitivity following BFRT training every two weeks for eight weeks (Kambič et al., 2019). In contrast, an additional study suggests improved metabolic control in patients with type II diabetes secondary to improved muscle mass, metabolism, and decreasing insulin levels (Saatmann et al., 2021).

A systematic review investigating the usefulness of blood flow resistance training with various neurologic conditions (Vinolo-Gil et al., 2022) found that BFR could be a beneficial rehabilitation tool for several pathologies, such as Parkinson's disease, stroke, multiple sclerosis, cerebral palsy, and spinal cord injury. Improvements were noted for (Vinolo-Gil et al., 2022)

• Sensorimotor function
• Frequency and step length symmetry
• Perceived exertion
• Heart rate and gait speed
• Walking endurance
• Fatigue
• Quality of life
• Muscle thickness
• Gluteus density
• Muscle edema

No improvements were found in lower limb balance. Studies involving neurologic conditions have been few; many were case studies or involved low participant numbers, and more clinical trials are needed. Additionally, protocols for using BFR with neurological patients have not been developed.

Pain is a common problem for many patients participating in rehabilitation and can be a significant limiting factor in many cases. Many interventions are geared specifically toward pain modulation. Many patients have difficulty performing moderate-intensity exercise because of pain; therefore, their activities are limited and devised in a way to avoid pain. In 2018, Korakakis et al. (2018) found significant pain reduction in anterior knee pain with functional activities following BFRT and low-intensity exercise. Pain reduction was sustained for at least 45 minutes following the occlusion training. This could suggest a clinical application of BFRT as a precursor to other activities within a rehabilitation session, providing clinicians a window of opportunity for knee-loading activities (Korakakis et al., 2018), thus leading to greater compliance and consistency of physical therapy activities (Hedt et al., 2022). The mechanism of pain reduction is still unknown. Still, theories revolve around "opioid and endocannabinoid mediated pain inhibition, recruitment of high threshold motor units, exercise-induced metabolite production and an interaction between cardiovascular and pain regulatory systems" (Hedt et al., 2022).