Introduction

In Part 1 of this series on recalcitrant wounds, we started our discussion on some factors on why wounds may seem to stall or stop healing. It can be very difficult in trying to treat a wound that seems to resist all efforts to get it to heal. In Part 1, we discussed some signs of a recalcitrant wound, exploring alternative etiologies behind a wound and how dressings can impact a wound’s ability to heal.

In Part 2, we will discuss other possible factors that can cause a recalcitrant wound, including, infection, prolonged or chronic inflammation, the presence of necrotic tissue, the edge effect, nutrition as well as socio-economic factors. We must also bring up the fact that, due to underlying comorbidities or complications, some wounds may never heal and how to start a conversation about this.

Infection

An underlying, untreated infection may cause wound healing to stall. There are varying degrees of pathogen growth on a wound that can be part of the natural microbiome of the wound. All wounds have some amount of microbes on their surface, and this often represents healthy colonization, which may actually have a positive effect on the wound. Healthy bacteria can live synergistically on the wound and have no negative impact on the healing process. However, if the growth of the pathogens start to increase, the wound may become critically colonized. Signs of this can include excessive exudate, a sudden decline of previously healthy new tissue, increased or persistent necrotic tissue, and increased signs of inflammation. You may also see greater friability and easy bleeding of the wound. The wound may start to develop an odor. This may be treated with a topical antimicrobial based on a wound culture. At this point, we can also consider dressings that are impregnated with antimicrobial agents, such as silver, iodine, or honey.

If the critical colonization of microbes progresses to wound infection, it can lead to deeper or even systemic infection. At this point, you will begin to see systemic signs of infection, including elevated temperature, malaise, and fatigue. The wound itself will become larger, may develop new areas, and may involve underlying structures.¹ At this point, systemic oral or intravenous antibiotics should be utilized.

Inflammation

Inflammation is a natural part of the healing cycle and is essential in wound healing. This is the phase where there is a sudden increase in specific cell types to the wound. We see a surge of neutrophils to the site, and this allows for the cleanup of any debris and pathogens and the removal of any damaged tissue. Cytokines and growth factors are released at this time, and they begin to activate fibroblasts, promote angiogenesis, and trigger endothelialization. It is at this time that matrix metalloproteinases (MMPs) appear and help remove damaged tissue, loosen the attachment of biofilm at the wound bed, and degrade the basement membrane around capillaries, thereby allowing for the new growth of healthy blood vessels.¹

All of these actions comprise an essential part of the inflammatory process. Think of a building that had been set on fire. That building will need to have a construction crew show up and clear away any damaged material before they can start to rebuild. However, that crew can’t be at the site demolishing the structure forever or nothing will get built in its place. If we begin to see chronic MMPs in a wound, the wound can stop healing and become “stuck” in the inflammatory phase.

If present for too long, the MMP “crew” can cause destruction to any new proteins and growth factors and delay healing. Removing these MMPs by debriding the wound regularly or using a negative pressure wound vacuum can help bring about the next phase of wound healing, proliferation. In this phase, we see the growth of new granulation tissue and epithelial formation. You may have a wound that is debrided regularly and is still stuck in the inflammatory phase. It is important to keep in mind that some treatments can actually promote inflammation and therefore may cause a prolonged inflammatory phase and become cytotoxic (will kill healthy cells). These products should be used judiciously and not for more than 2 weeks. Examples of anti-inflammatory agents include:

• Polyhexamethylene biguanide (PHMB) gauze or foam
• Gentian violet or methylene blue foam
• Silver and honey-based products (for short period of time)
• Systemic nonsteroidal anti-inflammatory drugs (NSAIDs)

Necrosis

If a wound has persistent necrotic tissue, this can also cause the wound to stall. The necrotic tissue can act as a physical barrier and prevent oxygen and nutrients to access the area. It causes an increase of MMPs in the area that can lead to a prolonged inflammatory phase.² Necrotic tissue also acts as an excellent medium for bacterial growth because it is high in sugars and protein. It can also produce increased exudate, which can lead to the breakdown of the wound or periwound. Necrotic tissue may often have a malodor that can make living with the wound difficult or embarrassing for the patient. Therefore, it is vital that wounds are debrided of any necrotic tissue regularly. Removing the necrotic tissue by surgical debridement to bleeding tissue will stimulate growth of healthy tissue.

Edge Effect

In a perfect world, the edges of a wound will steadily advance inward with new epithelial tissue growth. However, we don’t live in a perfect world, and the edges of the wound may not always act as expected. Sometimes, the edges fail to contract and migrate across the wound or even start to roll in under themselves, forming epibole or undermining along the edges. This can significantly stall healing time. Epibole can be managed with sharp debridement, application of skin grafts, or application of biological agents such as skin substitutes.³

Nutrition

When assessing a wound that doesn’t seem to be healing, it can be easy to overlook some more subtle causes that may be a factor. Much like any process in the body that requires new cellular growth, a wound has basic metabolic and nutritional needs. I’m sure any bodybuilder can tell you how important it is to ingest the right amount of macronutrients and micronutrients for optimal growth. A wound is no different. Wounds need at least an extra 30 calories/kg/day and 1.5 g/kg/day of protein.

Without the essential nutrients and calories, a wound will stall its healing trajectory or even decline. Some patients may not have access to or know about the nutrients essential for wound healing. In these cases, a referral to a nutritionist may be necessary. Checking laboratory values can provide insight into protein stores and needs. Checking albumin and prealbumin levels can indicate general nutrition status and alert you to potential malnutrition. Albumin is a sensitive marker of long-term protein deficiencies (18-20 days), whereas prealbumin is a more acute marker of short-term changes (2-3 days).⁴

Albumin

• 2.4-5.4 g/dL: normal
• less than 3.2 g/dL: poor outcomes

Prealbumin

• 15-36 mg/dL: normal
• The lower the number, the worse the outcome

Socioeconomic Factors

Most clinicians counsel their patients with the best of intentions. We may discuss optimal treatment strategies, suggest a perfect diet for healing, and recommend advanced dressings designed to maintain the best environment possible for the specific wound. Unfortunately, these best intentions may not be the best actual plan for the patient individually. Perhaps they feel unable to change the dressing themselves and will instead rely on someone else who may not be available as often as needed. Or perhaps that patient is unable to financially afford the dressings suggested.

Perhaps they don’t have a ride to attend regular office visits for serial debridement. Whatever the reason, the plan should be discussed in a nonjudgmental, straightforward manner that will allow for everyone involved to feel comfortable. Evaluate for any habits that could cause a delay in wound healing, such as smoking, substance abuse, or poor personal hygiene. Evaluate emotional well-being, access to care, the presence of an active social support system for the patient, or any financial restraints. Discussing these topics and then coming up with a strategy can empower the patient and will ultimately guide everyone toward an outcome that will impart a feeling of control over the wound.

Nonhealable Wounds

Although it’s sad to realize, some wounds, given their underlying etiology, the patient’s comorbidities, or an uncorrectable cause, may simply never heal. These wounds may never heal because of comorbid health conditions, poor circulation, or cancer, and surgical options may not be possible because of high risk of poor surgical outcomes. Nonhealing wounds are thought to account for roughly 5% to 10% of all chronic wounds.¹

In these cases, a conversation will need to be had between the provider and the patient. A candid discussion of realistic expectations and goal settings can lead to expectations of care that the patient may center around comfort and management rather than healing. Addressing pain management, prevention and/or treatment of infection, management of exudate and odor, and ways to optimize overall quality of life can give the patient a better outcome while still living with a chronic wound.

Conclusion

Recalcitrant wounds can be a major source of frustration for clinicians and patients alike. However, by going back to the basics and assessing why a wound has stalled can help you to develop a realistic plan on how to proceed. Consider the etiology of the wound, whether you are using the most appropriate dressings, and whether inflammation or infection is present. Does the wound have necrotic tissue present? Is the edge of the wound smooth and growing inward, or has it developed epibole?

Assess the patient’s nutritional status, and make sure to ask the hard questions around any socioeconomic issues that the patient may have. Determine whether the wound has the potential to heal, and if not, how can you help to create a plan that will maintain comfort and quality of life? With these steps in mind, treating a recalcitrant wound doesn’t have to be a cause of stress in a clinician’s practice and in a patient’s life.

References

1. Sibbald RG, Elliott JA, Persaud-Jaimangal R, et al. Wound bed preparation 2021. Adv Skin Wound Care. 2021;34(4):183-195.
2. Caley MP, Martins VL, O’Toole EA. Metalloproteinases and wound healing. Adv Wound Care (New Rochelle). 2015;4(4):225-234. doi:10.1089/wound.2014.0581
3. Dowsett C, Newton H. Wound bed preparation: TIME in practice. Wounds UK. 2005;1(3):58-70. Accessed March 14, 2022. https://www.woundsinternational.com/uploads/resources/content_9029.pdf
4. Doughty D. Why won’t some wounds heal? Adv Skin Wound Care. 2004;17(7):342-344.

About the Author

Becky received her BSN from the University of Vermont where, along with a love of nursing, she picked up a love of hiking and cross-country skiing. She moved to Massachusetts and started to work as a med-surg nurse at a busy Boston hospital. There, she found that she loved mentoring new nurses and returned to school to earn her MSN as an acute care clinical nurse specialist from the University of Massachusetts, Boston. She followed her love of teaching into the acute, sub-acute and university settings, but she found that she missed working directly with patients. She returned to school and earned her Post-Master's Family Nurse Practitioner Certification from Rivier University. It was shortly after this that Becky discovered her love for wound care. She worked part time in wound care and part time in family care while she earned her WCC certification. After several years, Becky decided to take her practice to the next level by opening her own LLC and is currently seeing patients for wound care and regenerative medicine. Becky's philosophy of “Never stop learning” has guided her in her practice and life. Her very supportive husband and daughter are her key inspirations to keep growing and trying new things. In her spare time, Becky loves traveling with her family, going on long walks with her dog, Echo, and reading historical and science fiction.