Background
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The effects of prehabilitation in preparation for and rehabilitation after interventional orthopedic procedures have received little attention in the literature.
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Exercise is a cornerstone of management prior to and following many orthopedic and surgical procedures.
Preprocedural Considerations
Prehabilitation is the practice of training and enhancing the patient’s functional capacity to prepare for a major procedure. Postoperative inactivity can lead to a decline in function, and the objective of prehabilitation is to help the patient withstand the stress of this inactivity.
In total hip and knee arthroplasty, preoperative functional status is a significant predictor of postoperative function. In fact, in one study, baseline pain and function was the single best predictor of pain and function at 6 months after a total hip or knee replacement. Patients may not report a perceived benefit from prehabilitation programs, , but studies have shown functional benefit. Even a 3-week preoperative strengthening program can increase lower extremity muscle strength prior to surgery and improve the immediate postoperative course. The significant strength gains achieved in the 3- to 6-week preoperative period suggest that the benefit of these short prehabilitation strength training programs is increased neuromuscular coordination and not necessarily strength. , Although there maybe short-term benefits to prehabilitation after arthroplasty, the longer-term benefits are unclear.
The literature on prehabilitation is more limited in other areas of orthopedics, but prehabilitation has been studied in anterior cruciate ligament (ACL) tears. Preoperative quadriceps strength is a significant predictor of knee function even 2 years after ACL reconstruction, and the enhancement of quadriceps strength and function preoperatively has been shown to improve surgical outcomes. In spinal surgery, prehabilitation showed no statistically significant difference in pain or disability, but patients reported feeling more prepared for surgery. These principles have not been studied in interventional orthopedics, but it is reasonable to believe that preconditioning could also have a beneficial effect after the varied procedures outlined in this text.
Nutrition plays a role in healing, has been studied in the trauma literature and is a concern in chronic wound management. Proper nutrition is an essential parameter in musculoskeletal health, including the prevention and treatment of diseases. This is likely underrecognized in elderly patients, and older adults may not have the same physiologic reserves of younger adults. Malnutrition is a risk factor for wound chronicity. Given the prolonged would healing process, nutrition should be considered as part of the presurgical or preprocedural assessment. Diagnostic markers of malnutrition remain elusive. The focus should be on basic nutrition and a healthy diet, including adequate calories and protein supplies to support the increased energy demands of collagen synthesis, angiogenesis, fibroblast proliferation, tissue remodeling, and wound contraction during the healing process. Protein deficiency has been associated with impaired fibroblast proliferation and collagen synthesis. Adequate hydration can help to promote tissue perfusion, oxygenation, and waste removal, and macro- and micronutrients may assist in enhancing the healing process. In the literature on wound healing, there is evidence for supplementing vitamins A and C and—if there is a deficiency—supplementing arginine, glutamine, and zinc. But the literature on orthobiologics is limited.
Malnutrition can take different forms; in addition to specific nutrient deficits, it can include inadequate intake and overconsumption. There is evidence that obesity and associated disorders can affect stem cell function. Obesity and diabetes have been associated with abnormal cytokine signaling, impaired tissue repair, and delayed wound closure. In rodent models of type 2 diabetes, endogenous mesenchymal stem cells (MSCs) were less effective at mobilizing to a site of injury than those in the nondiabetic controls, and high levels of glucose were associated with the reduced growth of mesenchymal progenitor cells. High glucose concentrations have been shown to reduce the osteogenic and chondrogenic potential of adipose-derived mesenchymal stem cells (ADSCs), and ADSCs had a reduced differentiation potential and a lower capacity for spontaneous or therapeutic repair in patients who were obese and had metabolic syndrome. In contrast, caloric restriction is known to reduce inflammation and has been shown to increase the proliferation of MSCs in mouse models , ; moreover, the restriction of glucose improved the self-renewal and antisenescence abilities of MSCs. Although the role of obesity or calorie restriction on clinical outcomes in orthobiologics is unclear, the literature suggests that calorie restriction may improve stem cell function.
Education has also been shown to have a positive impact on the outcomes of total knee and hip arthroplasty. , Being able to counsel patients regarding the expected postprocedural course can help them to prepare for the procedure. In theory, it could also affect the outcome after any interventional procedure. The following section outlines the expected postprocedure course of many orthobiologic procedures.
Postprocedural Considerations Basic Science
The healing potential following orthobiologic injections will vary depending on the tissue type (e.g., tendon, ligament, muscle, bone), underlying pathology (e.g., tendinopathy vs. tear), and anatomic location (e.g., Achilles vs. rotator cuff). In general, healing of tendon, ligament, muscle, and bone injuries follows the normal wound-healing cascade—a complex series of events that is typically divided into three phases: inflammatory, proliferative and maturation or remodeling. Some authors may describe a fourth phase, that of hemostasis, which is characterized by vasoconstriction and the formation of a blood clot immediately after an injury ( Fig. 37.1 ).
There is limited evidence-based literature on the role of rehabilitation following orthobiologic or regenerative procedures. , Although rehabilitation is often encouraged for the management of many orthopedic conditions to improve range of motion (ROM), strength, and functional activities, it may play a more specific role after orthobiologic procedures. The objective of many regenerative procedures is to trigger a healing response and stimulate the body’s own repair mechanism. Animal models of injury and repair are the primary means of understanding the fundamental process of healing in tendon, ligament, and muscle tissue. In a study by Virchenko and Aspenberg, rats with iatrogenically injured Achilles tendons were injected with platelet-rich plasma (PRP). Half of them received an intramuscular injection of botulinum toxin A (Botox) into the calf muscles to unloaded the tendon and had no effect from the PRP injection at 14 days compared with the control rats, who were not treated with botulinum toxin and did show neotendon development. The failure of the rats treated with botulinum toxin to develop neotendons suggests that mechanical stimulation is important in the early phases of tendon regeneration. Ambrosio et al., in a mouse model, demonstrated that stem cell transplantation into injured skeletal muscle proliferated and terminally differentiated toward a myogenic lineage with daily treadmill running, whereas the transplanted stem cells failed to divide rapidly in the absence of loading. Clinical studies have also supported the role of rehabilitation. In a pilot study of PRP for chronic patellar tendinopathy, Kon et al. found that subjects who did not follow the postprocedural stretching and strengthening program had poorer outcomes.
Further insight is needed into the molecular and cellular response to therapeutic exercises and stress after regenerative therapies. Based science studies showing that the effects of PRP are lost when tendons are unloaded mechanically, and one conclusion is that tendon healing may require a combination of biologic and mechanical factors. The term mechanotransduction is often used to describe the physiologic responses by which cells convert mechanical stimuli into structural adaptations. Mechanical stimuli or loads on a tendon are sensed by various cell surface receptors, integrins, stretch-activated ion channels, and other mechanisms, triggering cell–cell communication and changes in cellular biology within the cell nuclei. Eccentric exercises, with slow lengthening of the muscle-tendon unit while under load, have been shown to stimulate a cellular response, including the activation and proliferation of satellite stem cells. Heavy-slow resistance (HSR) training in which each repetition is performed slowly for more than 6 seconds for both the eccentric and concentric phases has shown similar results to eccentric strengthening in long-term pain reduction. HSR has demonstrated normalization of tendon fibril morphology. There is also interest in low-load resistance training with blood flow restriction (BFR), and recent studies have shown increased muscle proteins synthesis and proliferation of myogenic stem cells after BFR training. ,
There are many translational questions about how to apply these principles to orthobiologic procedures. The topic of tissue repair and rehabilitation is vast, and this chapter is by no means exhaustive. The goal is to understand the basic tenets of the healing process to help clinicians design rehabilitation programs, taking into consideration the patient and his or her pathology (e.g., mechanism of injury, tissue injured, severity, age of patient), the treatment (e.g., intra-articular vs. intraosseous or intratendinous vs. paratendinous), and the different phases of healing ( Table 37.1 ).
When rehabilitation after a regenerative procedure is being initiated, the following considerations, which align with the phases of the healing cascade, should be considered with each phase:
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Rehabilitation recommendations can vary depending on the tissue treated. For example, tendons require loading in an earlier phase of rehabilitation in order to help support the development of tensile strength. Overall, the literature suggests that mechanical stress on the tendon is needed to optimize outcomes. In contrast, osseous healing may require even longer periods of unloading and protected weight bearing. The severity of pathology should also be considered. For example, strengthening exercises after the injection of PRP may be started later in high-grade partial tendon tears as compared with tendinopathy.
Guidance following a procedure must also be tailored to the injectate or treatment. For example, rehabilitation following an injection around a tendon (e.g., a high-volume injection between the Achilles tendon and the Kegar fat pad) will have a different expected postprocedural course than an intratendinous procedure (e.g., PRP injected into the Achilles tendon). Likewise, an intra-articular knee injection of cortisone will have a different course than an autologous cellular injection.
Phases of Rehabilitation and The Healing Cascade
Phase I of Healing—The Inflammatory Phase (0 to 5 Days)
The inflammatory phase is the initial response to tissue damage and generally occurs within the first 5 days after injury. This phase is initially characterized by hemostasis and “walling off” of the injured site, increased vascular permeability, and an influx of inflammatory cells. Platelets are among the first cells to respond to an injury; they form a hemostatic plug and secrete chemokines (e.g., epidermal growth factor [EGF], fibronectin, fibrinogen, histamine, platelet-derived growth factor [PDGF], serotonin, and von Willebrand factor). These factors recruit macrophages to the healing site, resulting in the scavenging of debris and in phagocytosis to debride the wound bed. Fibroblasts also migrate to the wound in this phase, initiating the formation of granulation tissue and the transition into the proliferative phase. The specific cellular events will differ depending on the anatomy and physiology of the given tissue.
During this phase, patients may experience varying degrees of pain, swelling, redness, and limited ROM. Some patients’ symptoms are due primarily to laxity of the ligaments; if such individuals are treated, the initial swelling may sometimes actually cause a temporary improvement in perceived in stability and a reduction in symptoms, both of which dissipate once the swelling has gone down.
Phase II of Healing—The Repair Phase (5 to 21 Days)
The proliferative (granulation) phase is characterized by “rebuilding” of the local tissue, and generally lasts for several weeks after injury. Granulation tissue formation, collagen deposition, and angiogenesis create an extracellular matrix and network of blood vessels to supply the area. Neovascularization helps to supply the wound bed with nutrients. Macrophages continue to supply growth factors, and fibroblasts differentiate and produce collagen, depositing and remodeling the extracellular matrix.
Initially, migrating fibroblasts will begin to synthesize collagen around day 5, but by the fourth week, there is a noticeable increase in the intrinsic proliferation of fibroblasts from the endotenon. Initially the collagen fibers are randomly oriented, but as the tissue starts to mature, the collagen fibers are increasingly oriented along the direction of force through the tendon, increasing the tensile strength of the tendon. By week 5, tenocytes become the main cell type.
During this phase patients should feel a decrease in the initial postinjury/procedural pain. Preprocedural symptoms may persist, slowly improve, or wax and wane.
Phase III of Healing—The Maturation Phase (21 Days to 12 Months)
The maturation or remodeling phase starts 3 weeks after an injury and lasts up to 12 months or longer, with collagen deposition by fibroblasts continuing for this entire period. Increased stability is acquired during the remodeling phase and is stimulated by continued use of the tendon. Mechanical stress influences cell signaling and behavior; it contributes to remodeling of the collagen matrix and increases the tensile strength of the tissue. As the maturation process continues, the collage fibers continue to be reabsorbed and synthesized along the direction of force and cross-linking of the collagen fibrils occurs, increasing the tendons’ tensile strength. Along with this, there is increased deposition of type I collagen in preference to type III collagen. , The tensile strength is estimated to reach its maximum at 3 months , but never fully returns to its preinjury strength. During this period, patients are usually noticing a consistent improvement in symptoms, although their condition will still often wax and wane as tissue transitions from granulation tissue to scar formation.
Tissue-Specific Considerations
Tendons and Ligaments
Healing of tendons and ligaments follows the three phases of wound healing that have already been detailed. In the initial phase, blood clot and granulation tissue fill the gap between the tendon and ligament fibers. In tendons, fibroblasts and tenocytes in the epitenon and paratenon are recruited and proliferate, bridging the injured gap and forming a stable scar. In the early stages, the matrix is composed of increasing amounts of type III collagen. After 10 weeks, a higher proportion of collagen type I is synthesized and type III collagen decreases, forming scarlike tendon tissue, a process that will continue for years. ,
Muscles
Muscle strains that cause a rupture of the myofibers also go through the three phases of healing. Satellite cells begin to proliferate and form new myoblasts, which fuse into myotubes within a couple of days. Similar to tendons and ligaments, fibroblasts produce collagen and form scar tissue to bridge the gap between muscle fibers.
Cartilage
Articular cartilage has poor intrinsic healing capacity and generally does not heal or heals only partially under certain conditions. In most cases, surgical or biologic interventions are necessary to induce a repair response. Treatments include debridement, microfracture, and autologous tissue transplantation (e.g., autologous chondrocytes or MSCs). Little is known about the histologic effects of cartilage healing after these procedures. In vitro studies have demonstrated that mechanical stress can stimulate the differentiation of MSCs into chondrocytes, extracellular matrix synthesis, and cytokine secretion, whereas excessive stress may cause cell death and matrix degeneration.
Bone
Injured bone (e.g., fractured or necrotic bone) is resorbed and replaced by new bone following the three phases of healing. Macrophages and osteoclasts remove injured calcified bone, and osteoblasts fill the fracture gap, forming granulation tissue. Delayed bone formation and nonunion have been attributed to variations in the local inflammatory environment as well as the recruitment of muscle-derived stromal cells and osteogenesis early in the healing process. Bone repair follows two phases of healing: (1) the initial cartilaginous soft callus, followed by (2) remodeling and formation of a bony hard callus. Initially, the soft callus is formed when adjacent soft tissue and periosteum bridge the fracture site, stabilizing the fracture. Osteons travel along the cortical bone (by the Haversian system); they bridge the fracture gap, , and osteoblasts synthesize woven bone, resulting in a hard callus. , , This irregular woven bone callus remodels over months to years through continuous osteoclast resorption, while osteoblasts replace the matrix with lamellar bone to bring the bone back to its original shape, size, and strength/stability.
Overview of Rehabilitation Guidelines per Phase of Healing
The objective of many traditional orthopedic injections, such as corticosteroids or ketorolac injections, is to address inflammation. The objective of orthobiologic procedures in interventional orthopedics is different, and the aim is to reduce pain and improve function. This is often achieved by stimulating a healing response by delivering growth factors to the target tissue (e.g., PRP, autologous stem cells) or controlled microtrauma to convert a chronic injury into an acute injury with healing potential (e.g., prolotherapy, percutaneous needle tenotomy, Tenex ultrasonic debridement).
The literature on rehabilitation after orthobiologic or interventional orthopedic procedures is limited, and many of the rehabilitation protocols that have been proposed constitute attempts to translate these would-be healing principles into clinical practice. , There is some variability in the duration and overlap of the phases of wound healing described in the literature, and progression through the rehabilitation process should be informed by clinical progress through the program, and individualized, reflecting the type of tissue undergoing recovery (e.g., tendon, bone, ligament, muscle), severity of the underlying pathology, the patient’s preprocedural fitness level, her or his physical abilities, and any existing comorbidities.
Rehabilitation in the Inflammatory Phase of Healing (0 to 5 Days)
The goal of rehabilitation in the inflammatory phase is typically one of protection, and care typically focuses on managing pain and postprocedural swelling. Management may vary, depending on the procedure, and tissue type (i.e. tendons, ligament and bone/cartilage) but is typically achieved with immobilization or bracing, ice, elevation, medications, and gentle ROM exercises to activate the vasomotor pump.
Immobilization/Bracing
In most cases, protected weight bearing is recommended for pain control in the first 1 to 3 days. Most randomized controlled or prospective studies on orthobiologic procedures have prescribe a period of absolute or relative rest during the acute inflammatory phase, although no prospective studies have specifically studied these rehabilitation protocols. Immobilization should not be prescribed owing to a concern that the administered orthobiologic may disperse to other locations with movement. In a cadaveric model, Achilles tendons that were injected with blue dye to simulate a PRP injection were manipulated through 100 cycles of ankle dorsiflexion and plantarflexion, resulting in no significant difference in the spread of the dye compared with control specimens that were kept in a prone resting position for 15 minutes after the injection. This suggests that early motion does not increase the spread or clearance of PRP from the target site.
Limitation of joint motion can help to reduce pain in the associated area, and weight-bearing restriction or bracing can be used for this objective. Avoiding any pain-provoking activities is a common recommendation, but recommendations have varied across the literature, from avoiding all physical activity to limiting only repetitive movements. Crutches, a controlled-ankle-motion walking boot, or unloader braces can be used to limit motion or decrease stress on a joint, bone, or tendon/ligament after treatment. Any period of immobilization should be limited and guided clinically. In most randomized controlled or prospective studies that detailed postprocedure protocols, patients were usually instructed to restrict weight bearing or to immobilize the joint for 3 days to 2 weeks. However, there is a concern that immobilization may have a negative impact on tendon healing. In animal models, loading the tendon resulted in neotendon development after a PRP injection versus when the tendon was unloading, there were no beneficial results. Prolonged immobilization has been associated with joint contractures and functional impairment, and early gentle active ROM is considered safe.
Pain Management
Postprocedural pain can vary among patients and procedures. For example, intra-articular injections are often less painful than intratendinous or intraosseous injections. Periprocedural nerve blocks, when possible, can help with acute postprocedural pain management. Longer-acting anesthetics, such as ropivacaine, can extend the efficacy of these blocks. Alternative approaches to pain management and analgesia include cryotherapy and nonsteroidal antiinflammatory drugs (NSAIDs).
There are different methods of cryotherapy, including the use of crushed ice, ice bags, chemical or gel packs, and commercially available cryotherapy devices that provide the continuous circulation of ice water. However, there is evidence that some of these methods are more effective than others. There is some debate on the issue of limiting cryotherapy in the acute phase after an orthobiologic procedure. , Cryotherapy has been shown to be effective for managing pain in certain situations and is often accepted as an integral part of the treatment of acute soft tissue injuries despite the lack of a robust evidence base. In one review of regenerative procedures for tendinopathy, 20% of prospective randomized controlled studies prescribed cryotherapy for pain management. The theoretical concern is that cryotherapy may reduce blood flow, which is important for healing. However, the literature is limited and the effect of cryotherapy depends on a number of factors, including the temperature of the cooling device, the depth of the subcutaneous tissue, and the frequency and duration of treatment. , Studies have shown that cryotherapy can temporarily decrease microcirculatory perfusion when measured at a depth of 2 to 8 mm, , but they disagree on whether this decrease in blood flow persists following active cooling. , There is limited literature on how the superficial effects of cooling affect the perfusion of deeper structures, and skin temperature has been shown to be a poor predictor of intramuscular temperature and may be a poor predictor of perfusion to deeper structures. In one study of cryotherapy on the microcirculation of the midportion Achilles tendon, the authors showed reduced blood flow within the first minute of cryotherapy and return of capillary blood flow during recovery. Another theoretical concern is that cryotherapy may decrease platelet activation, but in vitro studies have shown that the temperature did not affect platelet adhesion when tested at 0 and 37°C.
The limitation of NSAIDs before and after an orthobiologic procedure is widely accepted across the literature. NSAIDs have been shown to inhibit platelet function and reduce the release of growth factors. In a study using a rat animal model of a surgically repaired rotator cuff tendon, even initiating NSAIDs in the proliferative stage of healing decreased the biomechanical strength of the repaired tendon.
Non-NSAID pain medications and prescription narcotics are often prescribed for the first 72 hours. Over-the-counter acetaminophen is often acceptable for pain control after most procedures and does not demonstrate any antiinflammatory activity. Narcotics can be used for breakthrough pain following opioid-risk mitigation strategies, including patient education about opioids, clear instructions about when to use opioids (e.g., for moderate or severe pain only), and prescribing short-acting opioids at the lowest dose necessary. In geriatric patients, doses should be decreased by at least 50% if there is concern for cognitive impairment, risk of falls, respiratory dysfunction, or renal insufficiency.
Rehabilitation in the Proliferative Phase of Healing (5 Days to 6 Weeks)
The objective of rehabilitation in the proliferative phase is to gradually increase activity. There is no consensus on the optimal timing of a stretching or strengthening program, and most published study protocols do not specify the type of strengthening recommended. Rehabilitation in this phase is progressive and is typically governed by patient’s tolerance. A good guideline is to limit any activity that increases the patient’s pain to greater than a 3/10 during or after that activity.
Intraosseous, intraarticular, axial and injections of tendons and/or ligaments may all require different periods of rest and activity modification. , The literature on tendon healing clearly suggests that early controlled loading influences the early phases of tendon healing after regenerative injection or microtrauma (needle tenotomy) , and that appropriate mechanical loading induces the differentiation of tendon stem cells (TSCs) into tenocytes. However, excessive loading can induce the differentiation of TSCs into adipocytes, chondrocytes, and osteocytes. Concerns about heterotopic ossification after PRP , in theory may stem from the failure of rehabilitation rather than the orthobiologic injection.
Stretching
In the literature, the timing of a stretching program has ranged from 24 hours postprocedure to 1 week. Studies have been performed to determine if dynamic stretching (DS), static stretching (SS), or proprioceptive neuromuscular facilitation (PNF) were superior; however, there is no consensus on the best form of stretching in early phases of healing. The literature on DS, SS, or PNF in sport shows a small to moderate effect on performance and a similar improvement in ROM with all of the stretching approaches. There is no overall effect on injuries prevention with SS and PNF, but no data is available for DS on injury prevention. For tendinopathies specifically, it is inferred that static stretching is the “safest” form of stretching due to its slow and steady nature. ,
Strengthening
Strengthening during the proliferative phase has also been evaluated after regenerative procedures in tendinopathy. This is typically started at 2 weeks in most published postprocedure protocols, , but timing varies across the literature. For joint injections, the strengthening program likely can be start sooner than with tendons or ligaments. Most recommendations are to have a progressive strengthening program. This is based on the progression of healing in tendons, where initially newly synthesized collagen fibers are oriented randomly, but as the proliferative phase progresses, the collagen fibers are increasingly oriented along the direction of force, thus increasing the tensile strength of the tendon.
The safest type of contraction in this phase of healing may be isometric, since joint motion is limited. Isometric contractions can decrease blood flow to the active tissues, but the effect is likely temporary. Isometric exercises have also been shown to be effective for short-term pain relief, and the authors typically will initially start with isometric strengthening exercises after a regenerative procedure. ,
Eccentric contraction or heavy slow resistance training may be the most beneficial type of exercise for long-term pain reduction and functional improvement in tendinopathy, but it has not specifically been studied after regenerative injections. Limited literature guides the ideal timing to initiate eccentric strengthening. There is some concern that if eccentric strengthening is started too soon, it may have a hypovascular effect that attenuates the healing cascade, and it has been suggested that eccentric exercises should be reserved for the late proliferative or remodeling phase. There is also limited literature on open-chain versus closed-chain exercises after regenerative procedures. ,
Rehabilitation in the Remodeling Phase of Healing (6 Weeks to 12 Months)
The goal of rehabilitation in the remodeling, or maturation, phase is the safe return to higher-level activities and sport. At this stage, patients should have completed the early rehabilitation protocols and have full ROM across the joint. Eccentric strengthening should be started in this phase, if not initiated earlier during the late proliferative stage, and proprioceptive exercises should be added to the rehabilitation program.
The literature is limited to guide return-to-play decisions; the timing should be individualized to the athlete. Initially, there should be a focus on the reintroduction of functional activities specific to the athlete’s sport. Patients with lower extremity injuries can start jogging and progress activity as tolerated as long as the pain does not increase greater than a 3/10 on numeric rating scale. Sport-specific movements and activities should be included in a controlled setting before progressing to a practice or game/competition setting.
Conclusion
Postprocedure recommendations are based on the underlying physiology of the healing cascade and the relative time frames at each stage of healing. Suggested rehabilitation protocols are general guidelines ( Table 37.1 ). Ultimately the rehabilitation protocols will have to be individualized to best benefit each particular patient in terms of the specific injury and treatment. Table 37.2 provides examples of protocols for knee, intra-articular ( Table 37.3 ), rotator cuff intratendinous ( Table 37.4 ), ACL intraligament ( Table 37.5 ), and hip intraosseous ( Table 37.6 ) orthobiologic procedures.
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