Exercise and Chronic Wound Healing

The calf muscles have been called the body’s “second heart,” improving blood circulation when exercised, usually by walking. Structured exercise training (SET) increases calf muscle pump function, lower limb circulation, and walking capacity for those with limited ambulation due to peripheral arterial disease (PAD)¹ or venous insufficiency.² This resulted in the Centers for Medicare and Medicaid Services (CMS) decision to reimburse up to thirty-six 30- to 60-minute, properly supervised hospital outpatient or office-based SET sessions over 12 weeks to treat intermittent claudication for patients with PAD. Exercise improves acute wound healing in diabetic mice³ and healthy elderly humans,⁴ but insufficient evidence supports its healing efficacy on ischemic ulcers,¹ venous leg ulcers (VLUs),⁵ and diabetic foot ulcers (DFUs).⁶ This month’s Evidence Corner examines 2 recent randomized controlled trials (RCTs) testing the effects of foot exercises that activate calf muscles on chronic VLUs⁷ and DFUs.⁸

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Reference: O’Brien J, Finlayson K, Kerr G, Edwards H. Evaluating the effectiveness of a self-management exercise intervention on wound healing, functional ability and health-related quality of life outcomes in adults with venous leg ulcers: a randomised controlled trial [published online January 27, 2016]. Int Wound J. 2017;14(1):130–137.

Rationale: Despite evidence that exercise improves calf muscle pump function in those with venous insufficiency, there are few RCTs exploring exercise's effects on VLU healing.

Objective: The investigators sought to determine whether a home-based progressive exercise program facilitated by telephone contact improves VLU healing.

Methods: An open-label, 12-week RCT studied VLU healing rates, functional ability, and health-related quality of life (HRQoL) of individuals receiving usual care (N = 32) compared with those receiving usual care plus structured progressive resistance exercise (N = 31). All patients received usual care, consisting of evidence-based patient-appropriate wound care and compression. All were given activity diary worksheets completed during telephone calls at baseline and weeks 1, 2, 4, 6, 8, and 12; a pedometer; general leg care; motivational booklets; and telephone calls at the same time points without exercise-related goal setting or advice. The exercise group received added exercise advice and goal setting based on feedback from the patients’ exercise diary. Exercise goals started at Stage 1 with 10 daily repetitions of seated heel-rises for both legs, increasing by 5 repetitions after 3 days of successful completion. When exercise goals reached 25 repetitions, the patient progressed to Stage 2 for the same increasing schedule of standing heel-rises, followed similarly by Stage 3 with the same increasing schedule of 1-legged heel rises. Adherence to the exercise protocol was recorded on a Likert 0–2 scale during phone calls. The primary outcome was percent of ulcers completely healed at 12 weeks. Healing progress was measured as percent area reduction from baseline based on digital planimetry measures of ulcer area. Secondary measures were patient-reported activity measured using the Yale Physical Activity Scale, functional capability using the Tinetti Gait and Balance scale, ankle range of motion by goniometry, and HRQoL using Physical and Mental components of the Medical Outcomes Survey Short Form-8. Baseline demographics and VLU risk factors were tested for comparability. A Chi-square test of independence evaluated significance of differences between numbers healed in the 2 groups. A 2-way repeated-measures analysis of variance tested for group differences, in the remaining variables with an alpha error probability < .05 establishing statistical significance.

Results: Intent-to-treat analysis found 77% of the exercise group and 53% of usual care control patients healed during the 12-week RCT (P = .09). Patient-reported activity, functional gait and balance, ankle range of motion, and HRQoL improved over time similarly with no significant difference between the 2 groups. For the 19 patients who adhered to the protocol, completing walking or leg exercises at least 75% of the time, the group engaging in progressive exercise improved more than those receiving usual care on percent healed, activity, functional gait and balance, range of ankle motion, and the physical (P < .05) but not mental aspects of HRQoL.

Authors’ Conclusions: Study participants who adhered to a progressive exercise program as adjunctive treatment to usual VLU care were significantly more likely to heal their VLU in 12 weeks compared with those who received usual care alone. Improving adherence to exercise protocols is important for this population.

Reference: Eraydin Ş, Avşar G. The effect of foot exercises on wound healing in type 2 diabetic patients with a foot ulcer: a randomized control study. J Wound Ostomy Continence Nurs. 2018;45(2):123–130.

Rationale: Studies have reported that exercise improved neuropathy, circulation, balance, and gait functions in individuals with diabetes, but only one small pilot study⁶ explored the effects of exercise on DFU healing.

Objective: The authors examine the effects of foot exercise on individuals with type 2 diabetes mellitus and a DFU.

Methods: After appropriate institutional review board approval, a prospective, parallel-group RCT randomly assigned hospitalized patients diagnosed with a Wagner grade 1 or 2 DFU to receive either standard care (N = 32) or the same standard care without debridement and with added standardized foot exercises (N = 33). Standard care DFUs were cleansed with saline, covered with gauze, and received debridement and culture-guided antibiotics only if deemed clinically necessary. Offloading practices were not reported. Patients receiving healing agents were excluded. Those in the exercise group were instructed to perform 10 repetitions of 18 standardized nonweight-bearing foot and toe exercises twice daily. Each exercise was repeated in the sitting position before healing or standing position after the DFU healed. Standard care and data collection forms were provided to all patients. The exercise group also received 20 to 30 minutes of clinic-based standardized foot exercise demonstration, daily exercise diaries, instructions, and pictures. Patient consent and demographic data were recorded at enrollment and DFU area and depth were recorded at baseline and after 4, 8, or 12 weeks of the study. Adherence to the exercise protocol and extent of patient memory of the foot exercises were recorded twice during the study. Independent sample t tests (uncorrected for multiple comparisons), Mann-Whitney U, analysis of variance, and Kruskal-Wallis tests assessed group differences for continuous variables with χ² and Fisher’s exact test analyzing categorical variables. P < .05 indicated statistical significance.

Results: Intent-to-treat results were not reported. Among the 30 participants in each group completing the study, patient demographics were comparable. Baseline mean wound area of the control group (24.7 cm²) exceeded that of the exercise group (12.6 cm²) at baseline (P = .008). Both groups reduced in average area over time to 18.5 cm² (control) and 3.3 cm² (exercise). A repeated measures analysis of variance was not performed to test the significance of this clinically important difference between the groups in rate of area reduction over time. Only the exercise group reduced in depth by week 12 (P = .014), with no DFU debridement, infections, cultures, or antibiotics reported. In contrast, control patients’ DFU depth increased, with continued needs for debridement and culture-guided antibiotics. Patients differed widely in adherence to the exercise protocol. Those exercising more than 30 of the study’s 96 days experienced earlier significant DFU area reduction continuing from week 4 compared with those exercising less frequently who achieved significant DFU area reduction later at week 12. This result may have been revealed more clearly in a repeated measures analysis of variance.⁹

Authors’ Conclusions: Foot exercises improve DFU wound healing and should be considered as part of the healing plan.

These 2 studies^7,8 are important first steps toward identifying exercise as an important addition to chronic leg or foot ulcer treatment plans. Both studies reported significantly faster healing of chronic lower extremity ulcers for patients who engaged most in SET. As with pain-free and maximum walking improvement for those with PAD, both studies’ SET contracted the patient’s calf muscle. This suggests that the more patients engage in calf muscle exercise, the more and earlier they improve their chronic VLU⁷ or DFU⁸ healing. Peripheral arterial disease was minimized in the VLU study⁷ by enrolling only those with an ankle-brachial index (ABI) > 0.8 and was not reported in the DFU study,⁸ so it is not clear whether these SET interventions improved healing of wounds affected by PAD. Research needs to replicate these findings in larger studies, stratified or risk-adjusted for patients’ severity of PAD, carefully monitoring and assuring adherence to SET protocols. Studies are needed to determine how many repetitions of what exercises involving which muscles are needed to improve healing. Both studies^7,8 highlight important implications for research and practice.

Could added calf muscle exercise or effective calf muscle stimulation beneath appropriate VLU compression or DFU offloading improve circulation and healing? Recent research supports the safety of using total contact cast (TCC) offloading for patients with PAD indicated by an ABI or toe-brachial index as low as 0.55,¹⁰ but it is difficult to perform treadmill exercises or heel rises or flex one’s feet or ankles wearing a TCC. Perhaps standardized calf muscle activation (CMA) devices could improve adherence to exercise protocols for those unwilling or unable to engage in SET. Randomized controlled trials reported that CMA improved PAD patients’ lower leg hemodynamics and walking,^11,12 and a pilot case series determined feasibility of using CMA to heal chronic, nonhealing VLUs or DFUs in long-term care patients.¹³ This research may open a path to discoveries that saves limbs and lives of patients being swept up in the global tidal wave of PAD or those with a recalcitrant VLU or DFU; however, this can only be determined by rigorous research on the topic.