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Refractory Wounds: Systemic Factors Affecting Repair – Extrinsic Factors (Part 2 of 4)

Refractory wounds are a significant worldwide health problem, affecting 5 to 7 million people per year in the United States alone, as discussed in a prior blog. Wounds that fail to heal not only impact quality of life, but also impose a significant physical, psychosocial, and financial burden. Additionally, individuals with refractory wounds often experience significant morbidity and sometimes mortality. Wound infections and amputations are common in this population, and chronic conditions often exist as well.1

We’ve previously defined and discussed refractory wounds in depth, including assessment and management of these non-healing wounds. Additionally, we’ve identified and discussed intrinsic factors as they relate systemically in a stalled or refractory wound. In this blog, we will explore extrinsic factors that impact healing in refractory wounds. Extrinsic factors are those factors that impact us externally; they can also be defined as environmental sources that disrupt the healing process. Malnutrition, medications, irradiation (radiation therapy), chemotherapy, environmental stressors, and wound bioburden and infection are several examples of extrinsic factors present in refractory wounds. In each of the following sections, extrinsic factors along with brief management strategies or practice pearls will be discussed.


As mentioned previously, refractory or chronic wounds are often seen in individuals with chronic conditions. Chronic conditions are often managed medically, with the use of medications. For example, anticoagulants (warfarin, heparin, etc.), antiplatelets (clopidogrel, aspirin, etc.), and non-steroidal anti-inflammatory medications (COX-2 inhibitors, ibuprofen, naproxen, etc.) are three types of medications often used to manage chronic conditions. These medications, however, impact or disrupt the first stage of wound healing, platelet activation. Additionally, steroids, immunosuppressive agents, antiprostaglandins, and opioids all impact healing, especially when used long term.1

It is important to conduct medication reviews and reconciliation with your pharmacist, as part of your interprofessional team to manage and treat the patient holistically. Medication management should be discussed with the primary care provider to best make adjustments to manage the patient medically and allow for maximum wound healing potential, as able, weighing the benefits and risks of each medication.


Malnutrition, especially protein-calorie malnutrition and micronutrient deficiencies, may affect tissue repair. Having a nutritionist or dietitian on board is helpful in identifying and correcting macronutrient and micronutrient deficiencies. Nutritional management is a huge component in the ability to heal (or not heal) a wound.1 Encouraging meals, healthy snacks, and protein can assist with wound healing. Often, the dietitian or nutritionist can also recommend an appropriate nutritional supplement to assist with wound healing.

Radiation and Chemotherapy

Radiation may have latent effects on the skin for years to come after completion of therapy. The vessels and proliferative cells (fibroblasts) in the treatment area are persistently damaged over a course of time while the patient receives their prescribed course of radiation therapy. Radiation therapy may cause skin issues and also impact the body’s healing ability for many years later because of the lasting impact of tissue ischemia. Chemotherapy affects proliferation, impacting the ability for tissue to adequately repair itself. The prescribed duration and strength of the chemotherapy and radiation therapy course correlate with the healing cascade.

Typically, during chemotherapy and radiation treatments, we aim to keep the wound stable, with a focus on healing once these therapies are complete.1 Again, taking an interprofessional approach here and managing the whole patient with the multidisciplinary team leads to the best outcomes.

Psychosocial Stressors

Immune function is impacted by many variables. Depression and stress release hormones within our bodies that may negatively impact immune function. Cortisol levels are increased during stressful times (adversely affecting cytokine production and fibroblast proliferation, and increasing matrix degradation). Additionally, increased levels of cortisol can impact the growth hormone-somatomedin system, which can lead to poor outcomes in terms of healing. Alternatively, stress management strategies are associated with improved healing outcomes. Some examples include biofeedback, positive imagery, hypnosis, exercise, and sleep.1 Involving recreation therapy and including non-pharmacologic management of extrinsic factors in the plan of care can certainly help manage extrinsic factors that impact healing, such as stress and depression.

Wound Bioburden and Infection

Bacteria in a wound compete with fibroblasts and oxygen and can in turn disrupt or slow the healing process. Excessive bioburden, also known as critical colonization, can result in biofilm formation, which further impairs healing and increases the risk for a more aggressive infection. Effective wound management requires ongoing, detailed assessment and follow-up, as well as determining the appropriateness of antimicrobial dressings (for poorly healing or plateaued wounds or localized infection).1 It is important to consult with each member of the interprofessional team and take a multidisciplinary approach when managing the wound, by remembering to manage the whole patient, not just the hole in the patient. Identifying and treating a wound infection early on can help with better outcomes long term.


It is important to piece together all of the systemic factors impacting healing when looking at reasons why a wound is not improving within two to four weeks of evidence-based topical therapy and a comprehensive plan of care. In future blogs, we will be exploring and defining the remaining two common factors affecting tissue repair: iatrogenic factors and adherence.


1. Netsch, DS. Refractory wounds: assessment and management. In: Doughty DB, McNichol LL, eds. WOCN Society Core Curriculum: Wound Management. Philadelphia, PA: Wolters Kluwer; 2016:181-197.

About the Author

Holly is a board certified gerontological nurse and advanced practice wound, ostomy, and continence nurse coordinator at The Department of Veterans Affairs Medical Center in Cleveland, Ohio. She has a passion for education, teaching, and our veterans. Holly has been practicing in WOC nursing for approximately six years. She has much experience with the long-term care population and chronic wounds as well as pressure injuries, diabetic ulcers, venous and arterial wounds, surgical wounds, radiation dermatitis, and wounds requiring advanced wound therapy for healing. Holly enjoys teaching new nurses about wound care and, most importantly, pressure injury prevention. She enjoys working with each patient to come up with an individualized plan of care based on their needs and overall medical situation. She values the importance of taking an interprofessional approach with wound care and prevention overall, and involves each member of the health care team as much as possible. She also values the significance of the support of leadership within her facility and the overall impact of great teamwork for positive outcomes. 

The views and opinions expressed in this blog are solely those of the author, and do not represent the views of WoundSource, HMP Global, its affiliates, or subsidiary companies.