Incorporating Exercise as an Integral Part of Wound Management

  Technological advances spanning the last few generations have simplified many things in our everyday lives while creating a faster paced way of life. Unfortunately, as everything around us has seemingly gotten quicker, our population as a whole has become more sedentary. Society in general has become less active, and, not coincidently, the prevalence of diseases related to chronic wounds continues to rise as improvements to healthcare also continue to occur. That is not to say that the rise in complications such as diabetes and obesity can be solely attributed to these factors. Widespread improper nutrition and larger segments of the population that are struggling economically have played roles as well.

  Regardless of the reasoning, there is no denying that chronic inactivity and chronic disease rates across the US are alarming. According to the Centers for Disease Control and Prevention (CDC), the number of Americans living with diabetes or prediabetes has more than tripled in the last 30 years. An estimated 25.8 million (8.3% of the population) Americans have been diagnosed with diabetes or prediabetes.¹ The upward trend for obesity incidence is very similar with more than 35% of the adult population classified as obese based on height and weight.² Exercise has been widely documented as an effective measure to reduce the risk of heart disease, stroke, certain types of cancers, diabetes, obesity, and other diseases.³ Despite this, only 48% of adults meet the 2008 physical activity guidelines established by the CDC that call for a minimum of 150 minutes of moderate-intensity aerobic activity and strength training or a comparable amount of vigorous activity per week.⁴ These numbers support the need for wellness programs to reduce the risk of developing complications associated with inactivity. However, patients with comorbid diabetes and/or obesity as well as chronic wounds may pose unique challenges for providers because wounds, as manifestations of underlying disease processes in most instances, may also be indicators that the ideal timeframe to implement an exercise program for prevention of further health complications has passed. This does not mean that wound care patients should not be started on exercise programs. What it means is that the primary goal of exercise should be to promote wound healing.

  This article will examine the benefits of exercise for patients living with nonhealing, chronic wounds in an attempt to assist the practitioner in developing safe, effective exercise programs for their patients. Additionally, the benefits of incorporating measurable outcomes into an exercise prescription will be discussed.

Assessing Risks & Benefits

  For high-risk patients, such as those with a history of cardiovascular disease or conditions that can be exacerbated by exercise (eg, sickle cell), a risk-benefit analysis is necessary. It remains the practitioner’s decision as to whether or not the benefits, including promotion of wound healing, outweigh the risks of complications for this complex set of patients. When considering activity level, it is important to realize that a target range that is safe and effective should be based on each individual’s condition. For example, a patient with extreme deconditioning or debilitation may see improvements in cardiovascular endurance by walking with supervision through the halls of the wound clinic, while this same activity is likely to be at too low of an intensity to cause adaptations in a healthy individual. Conversely, a healthy individual may benefit from adding resistance training or stair climbing to an exercise program while this may be too intense for an unfit individual and can lead to injury.

  If the intensity of exercise falls below this range, no adaptations will occur and there will be no perceived benefit of the activity. Intensities above the safe level frequently result in fatigue, injury, or even death. In order to control activity level, many of the studies involving wound healing are animal studies. For instance, a study by Radek and colleagues controlled activity level by immobilizing the hind limbs of rats for 14 days prior to creating an excisional wound. The effects of immobilization revealed delayed wound closure and reduced wound vascularity at one week post-injury when compared to the non-immobilized group.⁵ This raises a question: If a lack of exercise can impair wound healing, is it possible to improve healing through exercise? And if so, what is the mechanism? There is a surprisingly small amount of research that has been performed with the goal of determining the effects of exercise on cutaneous wound healing, especially when compared to evidence that supports exercise promoting the healing of other tissues (tendons, ligaments, muscle, bone). Several older animal studies, two involving rats and one with rabbits, found wound strength to be greater in animals that used a continuous passive-motion machine or were allowed unrestricted exercise versus those who were confined to a cage.^6-8 A more recent study found aged mice that were exercised had significantly smaller wounds than aged sedentary mice up to six days post-wounding. Exercise consisted of treadmill running for 30 minutes per day at a prescribed intensity for three days prior to and five days after wounding.⁹

  Investigations involving an exercise intervention for humans have found similar results to the animal studies. A 2005 study by Emery et al randomly assigned healthy older adults to an exercise or non-exercise group for three months. One month after assignment, an experimental wound was created and healing was monitored. Subjects in the exercise group healed more than nine days faster, on average, than those in the control group.¹⁰ In contrast to the positive benefits of exercise described in the Emery article, an article by Whitney and Parkman did not find that a supplemental exercise program improved wound healing in the one-week period following total hip replacement surgery.¹¹ Although a positive effect on wound healing was not evident, the authors expressed concerns that the intensity of the exercise may have been too low to induce physiological changes. They also reported exercise likely benefited their recovery in some way since patients that exercised more were discharged sooner.

  Extrapolating the research results mentioned above to patients seen in most wound care clinics is complicated because most chronic wounds are of varying etiology while these studies focused on acute, surgically created wounds. Currently, the body of evidence supporting exercise as an intervention to promote wound healing for people living with chronic wounds is lacking. However, studies examining the cellular changes associated with exercise have been performed that may shed some light on this issue. In studies that found exercise to be beneficial compared to a non-exercise control group, the effects seemed to be most evident early in the healing process, but eventually those differences evened out. When the wound healing timeline is considered, it seems apparent that exercise affects the inflammatory phase of healing. Acute inflammation is a critical component of wound healing and serves an important physiological purpose of cleaning the wound of debris and bacteria as well as laying the groundwork for the proliferative phase of healing. When the normal inflammatory process is disrupted, it can cause problems in later phases of wound healing.

  Much of the inflammatory response is regulated by the contents of macrophages and mast cells that are released in response to injury. Among the contents critical to the inflammatory process are the pro-inflammatory tumor necrosis factor-alpha (TNF-) and a number of interleukins (IL), which can either promote inflammation, as in the cases of IL-1 and IL-18; reduce inflammation (IL-10); or have a dual role that is both pro-inflammatory and anti-inflammatory (IL-6).¹² In its simplest form, the inflammatory process can be thought of as a series of checks and balances between pro- and anti-inflammatory cells and cytokines. When a wound becomes stuck in the inflammatory phase, the balance is lost and healing is delayed. Animal and human studies have demonstrated the ability for exercise to increase the expression of anti-inflammatory factors and inhibit the expression of pro-inflammatory factors. In animal studies dealing with aged mice and obese rats, habitual exercise effectively reduced inflammation.^9,13 When obese rats with metabolic syndrome were compared to lean rats, the regulation of IL-6 and TNF-a was found to be impaired.¹³ As mentioned previously, the role of IL-6 is complex, as it is both pro-inflammatory and anti-inflammatory. The production of TNF-a stimulates IL-6, so it is often a marker of inflammation. However, in a form of negative feedback its presence inhibits further TNF-a production, classifying it as anti-inflammatory. In this particular rat study, regulation of TNF-a and IL-6 was improved following a 14-week treadmill exercise program indicating that less inflammation was occurring.¹³ Similarly, cytokine levels were also reduced with a moderate intensity exercise program in aged mice.⁹ Creatine kinase, TNF-, and monocyte chemoattractant protein-1, which are all markers of inflammation, were all lower than they were in the sedentary group. This correlated with faster wound healing overall, particularly in the early phases of healing. The amount of time it took for a 20% reduction in wound size in the exercise group was 51% faster than they were in the control group. Although the gap narrows, the time it took to reach 10% of the original wound size was still approximately 25% less in the exercise group.⁹

Considering Human Studies

  Studies involving humans have reported similar results to the animal studies. An investigation involving nearly 14,000 US participants found an increased amount of physical activity in adults associated with decreased C-reactive protein levels, lower white blood cell counts, and plasma fibrinogen levels as well as elevated albumin concentrations compared to sedentary individuals.¹⁴ All of the changes associated with exercise in this study are characteristic of a decreased amount of inflammation. A separate study by Starkie and colleagues used eight healthy, young, male subjects to examine the effects of rest, exercise, and an infusion of IL-6 on inflammation. Subjects received an intravenous bolus of E. coli endotoxin on all experimental days. Based on pilot data, the authors anticipated a doubling or tripling in TNF-a levels with the bolus, indicating an inflammatory response to the endotoxin. On days the subjects rested they experienced a significant increase in TNF-a levels, while these levels did not change on days they exercised or were infused with IL-6, which, as already mentioned, inhibits further TNF-a production. The authors concluded that IL-6 produced by the exercising muscles helps to mediate an anti-inflammatory response against the TNF-.¹⁵ Since the vast majority of wound care patients are not healthy, young men, the question as to whether exercise would have the same effect in a different population arises. Jankord and Jemiolo published a paper that examined the effects of exercise on inflammation in elderly men.¹⁶ Unlike the results from Starkie et al, they found the more active cohort to have lower IL-6 and increased IL-10 levels compared to the less-active group. In this investigation, the authors describe IL-6 as pro-inflammatory and IL-10 as anti-inflammatory. The data seem contradictory at first glance; with one study suggesting a lower IL-6 level indicates less inflammation while the other study makes the same conclusion about high IL-6 levels. As IL-6 has a dual role, it is possible that both conclusions may be correct. As exercise stimulates the production of IL-6, which in turn inhibits inflammation by mediating TNF-, it would make sense that higher IL-6 levels after acute bouts of exercise would reduce inflammation. If, on the other hand, repeated bouts of exercise limit inflammation, as suggested by the conclusions of the Jankord and Jemiolo study, then TNF- levels would be lower and would produce less IL-6 in response.

  In addition to promoting wound healing by reducing inflammation, as evidence suggests, exercise causes localized and systemic vascular changes that improve tissue oxygenation. Exercise and wounds are similar in that they both create a localized hypoxia that is a trigger for neovascularization. This effect is described by the exercise physiology principle of progressive overload, which claims the body will adapt to imposed demands. In the case of a wound, mild ischemia creates stress on the injured tissues and causes them to adapt. Exercise also causes mild ischemia in tissues being stressed, which results in a similar body response. Expansion of capillary networks and proliferation of endothelial cells have been demonstrated to occur with repeated bouts of exercise through the vascular endothelial growth factor (VEGF) pathway.17 With habitual exercise there is also an increase in the number of oxidative enzymes, meaning the muscle can work longer or at a higher intensity before becoming ischemic. A 2008 article by Roy and colleagues outlined the effects of exercise on tissue vascularization. In this review, they describe how many of the factors associated with the peripheral vascular changes occur through the actions of VEGF and nitric oxide (NO).¹⁷ When designing an exercise program, the goal is to stress the system enough so that the body will attempt to adapt to the new demand by improving the delivery of oxygen to the affected area — the goal of this being that the wound will demonstrate improved healing if it has more blood flow. Conversely, if the body is not stressed, oxygen demands will be reduced and the capillary network will decrease in size. When this occurs, less blood will be available to the tissues when they are stressed and exercise tolerance will be diminished.

Determining Exercise Safety

  To attempt to develop a standard template for an exercise prescription for all patients living with wounds would be at best less than ideal and at worst potentially dangerous. A safe, effective exercise prescription always begins with a comprehensive evaluation of the patient’s health. Wounds are often manifestations of underlying conditions such as diabetes, peripheral arterial disease, or heart disease, so it is important to consider these and other potential (or known) comorbidities when developing a plan. The first step is often a pre-participation screening. One of the simplest screening techniques involves the administration of a survey that the patient can answer during an initial clinic visit to determine risk stratification and whether medical clearance is needed prior to exercising. The Physical Activity Readiness Questionnaire for Everyone, a seven-question, self-administered survey, can be used to identify patients who may need to obtain clearance. If any concerns are identified in the general health section of the questionnaire, the respondent moves on to the next section of nine questions related to chronic conditions.¹⁸ Based on responses, a determination of whether it is safe to exercise is made. By analyzing the known risk factors for coronary artery disease, a patient can be stratified into a low-, moderate-, or high-risk group. The known factors outlined by the American College of Sports Medicine (ACSM) are family history of cardiac disease, cigarette smoking, hypertension, dyslipidemia, impaired fasting glucose, obesity, and a sedentary lifestyle. A high-serum HDL cholesterol is seen as a negative risk factor, as it decreases the risk of coronary artery disease.¹⁹ If a patient is deemed appropriate for exercise, a program that addresses the individual’s condition can be designed.

Developing Exercise Program

  There are four basic factors that must be considered when developing an exercise prescription: mode of exercise, intensity, duration, and frequency.

  Exercise mode may come down to a matter of patient preference, but certain factors such as balance issues due to loss of protective sensation, abnormal range of motion, and any other orthopedic problems should also be considered. For example, exercising on a bike, although less functional, may be favorable to treadmill walking for those with a diabetic foot ulcer from a weight-bearing standpoint. An exercise that is safe and readily available will facilitate compliance. Once the mode is selected, the clinician must determine the appropriate intensity, duration, and frequency of exercise. Exercise intensity can be monitored in multiple ways in an outpatient setting. Two of the most common that are often used simultaneously are the use of a rate of perceived exertion and target heart rate ranges.

  Rate of perceived exertion scales allow the exercising individual to report a subjective level of tolerance at any time. This scale could be used by anyone, but is most useful for patients whose heart rate does not respond as expected to increased exercise intensity. A common example of this is a patient on beta-blocker medications that blunt the heart rate response to exercise, thus preventing heart rate from being a good indicator of intensity. When heart rate does respond normally, a percentage of maximal heart rate or heart rate reserve is often used to determine appropriate exercise intensity. This method differs from the percent of maximal heart rate method in that it accounts for resting heart rate. In order to determine a safe intensity at which to exercise, first accurately determine maximal heart rate. The commonly used equation (220 – age = max heart rate) may be effective for healthy individuals, but for those with elevated risk for complications, a medically supervised submaximal or maximal exercise test should be performed to determine a safe upper limit. Figure 1 gives an example of heart rate reserve, or the Karvonen method can be used to calculate a safe exercise intensity level. The range of 40-85% of heart rate reserve used in the example corresponds to the ACSM recommendations for intensity.²⁰ This method has the advantage of being more accurate than calculating percent of maximal heart rate throughout the range.²⁰ A third method to prescribe an intensity level would be as a percent of the VO_2max; however, this is not used as commonly in clinical practice due to the difficulty in obtaining a true VO_2max.

  Regardless of the method used, an appropriate intensity should be identified for the warm-up, target range, and cool-down portions of the exercise session. The goal of a warm-up is to bring the heart rate from its resting level to the lower level of the target range. For the cool-down, the goal is to bring it back near resting levels.

Setting & Assessing Goals

  The ultimate goal of an aerobic exercise prescription is to cause the body to adapt to the imposed demands of exercise. As the body adapts, an activity that was once stressful is no longer stressful. In order for this to occur, exercise must be performed long enough to stress the aerobic system and often enough to maintain and improve upon gains made. In individuals with poor cardiorespiratory fitness levels, duration at target range may be very short initially when the warm-up and cool-down are factored in. The duration of exercise will be inversely related to the intensity, so those that are exercising at a lower intensity will require longer exercise sessions to achieve similar results. ACSM recommends building up to a minimum of 20-30 minutes of exercise per day, excluding warm-up and cool-down to improve aerobic fitness^.20

  In most cases, exercise performed 3-5 times per week is recommended, with those performing a low-intensity activity requiring more frequent bouts than individuals exercising at high intensities.²⁰ The idea that if three times per week is good, then six times per week must be better is often a notion that the clinician has to dispel with highly motivated patients. More injuries and/or fatigue may occur when people increase the amount of exercise too quickly or begin exercising much more frequently.

  In regards to wound healing, the goal of adding exercise to the care plan should be to improve functional status. Frequently, the wound may not be the factor that is limiting a person’s active participation in activities. In the instance of a deconditioned patient with a leg ulcer, it is likely that aerobic deconditioning prevents, say, grocery shopping, not the wound itself. A therapy plan that heals the wound but fails to address the functional activity level cannot be viewed as fully successful, as the individual will still be unable to participate fully in the activities that they choose. With the new Medicare G-codes for claims-based functional reporting, the issue of functional outcomes has been brought to the forefront of therapy. Utilizing outcome measures that are reliable and have been validated is a critical component not only for billing, but because it is an effective way to monitor progress. Simple tests such as the lower extremity functional scale, the six-minute walk test, and the SF-36,® to name a few, are frequently used in rehabilitation but are underutilized in the wound care setting as ways to document holistic changes. Without incorporating outcome measures it will be very difficult to objectively measure effectiveness of interventions to improve wound healing, including exercise.

  There are also many barriers to developing exercise programs for wound care patients. The amount of hands-on, one-on-one time, risk factors associated with underlying conditions, and concern for making the wound worse are all impediments to implementation. When done properly, however, introduction of an exercise program can be an effective tool in the management of not only risk factors but the management of inflammation in active wounds as well.

  Edward C. Mahoney is associate professor of physical therapy at Louisiana State University Health Sciences Center, Shreveport.

References

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15. Starkie R, Ostrowski SR, Jauffred S, et al. Exercise and IL-6 infusion inhibit endotoxin-induced TNF-a production in humans. FASEB Journal. 2003;17(8):884-886.

16. Jankord R, Jemiolo B. Influence of physical activity on serum IL-6 and IL-10 levels in healthy older men. Medicine & Science in Sports & Exercise. 2004;36(6):960-964.

17. Roy S, Khanna S, Sen CK. Redox regulation of the VEGF signaling path and tissue vascularization: Hydrogen peroxide, the common link between physical exercise and cutaneous wound healing. Free Radical Biology & Medicine. 2008;44(2):180-192.

18. Physical Activity Readiness Questionnaire for Everyone (PAR-Q+). Canadian Society for Exercise Physiology. Accessed online: www.csep.ca/english/view.asp?x=698.

19. American College of Sports Medicine. Chapter 2: Preparticipation Health Screening and Risk Stratification. In: ACSM’s Guidelines for Exercise Testing and Prescription, 7th ed. Philadelphia, Lippincott Williams & Wilkins, 2006, 21-35.

20. American College of Sports Medicine. Chapter 7: General Principles of Exercise Prescription. In: ACSM’s Guidelines for Exercise Testing and Prescription, 7th ed. Philadelphia, Lippincott Williams & Wilkins, 2006, 139-148.