The statistics are alarming. The morbidity and mortality associated with lower extremity wounds are high, and we are constantly exposed to new options to help heal our patients. The toolbox for the wound care clinician has expanded exponentially in the past decade and it seems as though we are learning more and more daily about the basic science behind wound care.
The choice of wound care modalities and products should be based on sound evidence-based medicine and various algorithms exist to help guide therapy. Many of the algorithms will separate patients into low risk and high risk based on existing comorbidities and vascular status. These algorithms also frequently suggest moving away from the standard of care in patients who do not meet the suggested benchmark of appropriate wound healing progress of 50 percent closure at four weeks.1 Many advanced modalities including hyperbaric oxygen treatment and advanced biologics are reimbursed at this period in patients demonstrating a lack of progression toward wound closure. Poorer outcomes are often associated with wounds that fail to close in a timely fashion.
There are several important studies and acceptance about when to initiate advanced modalities for chronic, non-healing wounds. However, little discussion focuses on the patients we should not use advanced modalities for or, equally important, when to stop utilizing advanced wound care modalities. The focus of this article is to address this clinical dilemma.
The treatment of lower extremity wounds with advanced modalities can be very expensive. Many treatments, devices and products have a very high initial cost. However, from a dollar standpoint, we know that wound healing is ultimately cheaper than amputation, not to mention better quality of life.2 Ideally, we would choose advanced modalities based on solid evidence-based medicine, ease of use/access and cost effectiveness.
The guidelines for initiation of advanced therapies are often clear. As a rule, one may begin using these modalities after standard management without significant progress toward closure. Using biologic skin equivalents as an example, the Apligraf (Organogenesis) product insert notes the product is “Indicated with standard diabetic foot ulcer care for the treatment of full-thickness neuropathic diabetic foot ulcers of greater than three weeks duration that extend through the dermis but without tendon, muscle, capsule, or bone exposure.”3 The Dermagraft (Shire Regenerative Medicine) product insert states it is “Indicated for use in full-thickness diabetic foot ulcers greater than six weeks duration, which extend through the dermis, but without tendon, muscle, joint capsule, or bone exposure. Dermagraft should be used in conjunction with standard wound care regimens and in patients that have adequate blood supply to the involved foot.”4
When clinicians use them appropriately, advanced wound care products like biologic skin equivalents can help achieve closure for chronic or difficult to treat wounds. Oftentimes, we utilize these products on our most comorbid patients such as the patient with diabetes and end-stage renal disease or marginal blood flow. Ironically, these are the same patient populations that are often excluded from clinical trials of advanced modalities. There is frequent debate over the question of dosing frequency for biologic skin equivalents and duration of therapy for advanced modalities. Financial implications and restrictions on maximal use pose additional challenges to wound care clinicians.
In light of these issues, we should give consideration to stopping therapy when there is a lack of response or even forgoing utilization of advanced modalities in cases in which wound closure and, more importantly, the ability to maintain closure is futile.
In regard to contraindications with biologic skin equivalents, Apligraf is contraindicated for use on clinically infected wounds.3 Apligraf is also contraindicated in patients with known allergies to bovine collagen or the components to the Apligraf agarose shipping medium. Likewise, Dermagraft is contraindicated for use in ulcers that have signs of clinical infection or ulcers with sinus tracts.4 Additionally, Dermagraft is contraindicated in patients with known hypersensitivity to bovine products.
The pivotal trials for each of these products excluded patients with compromised vascular status or Charcot arthropathy. However, these are not listed as contraindications for use. In fact, several algorithms exist to help guide therapy and it is often recommended that high-risk patients such as those with previous history of ulceration or amputation or those with Charcot arthropathy receive advanced wound care modalities even earlier.5 The rationale behind this faster movement to advanced modalities is justified by the known potential for difficult wound healing and associated morbidity in this patient population.
In the absence of any other studies in the advanced comorbid patient population, one should hopefully observe the same trajectories toward healing. Clinically, there may be a slower response but the same principles of weekly reassessment and critical examination for response to therapy are mandatory. The critical question still remains when to stop advanced modalities because the reality is that we will not be able to heal all wounds nor should clinicians be utilizing these resources in certain clinical scenarios.
Chronic wound maintenance or the “palliative wound care” model provides appropriate, standard care and maintains accepted tenets for treatment including pain management, offloading, infection prevention and a dignified quality of life.6 This may involve regular home healthcare visits for dressing changes and less frequent face-to-face visits. This has the added benefit of keeping patients in their homes and not overburdening caregivers with frequent travel to and from clinics.
The criteria for inclusion in this type of protocol may include patients who have received advanced wound therapies for a reasonable period (six to eight weeks) with no progression towards healing. Additionally, a small percentage of wounds may not heal without surgical intervention. There may be cases in which the deformity underlying the etiology of the wound is too rigid and one is unable to accommodate it with external offloading. However, when it comes to patients who refuse or are deemed too sick or medically unstable to undergo surgical intervention for wound healing or amputation, clinicians may consider palliative wound care. Other potential “red flag” patients for whom advanced modalities may not be appropriate include smokers, the homeless, those with unstable mental illness and people with significantly elevated HbA1c.
Little is written about stopping advanced therapy use in wound care. As clinicians dedicated to healing patients, we often see it as a failure when we are unable to achieve wound closure. Ultimately, success should not be defined by the ability to close a wound but rather in providing the patient with optimal quality of life.
The first case concerns a 74-year-old male veteran treated for a chronic ulceration to the plantar central aspect of a Chopart amputation stump. His history includes diabetes mellitus, hypertension, coronary artery disease following three vessel coronary artery bypass grafts, dyslipidemia, chronic lower extremity edema and peripheral neuropathy. In 2009, he presented with osteomyelitis of the right fifth ray, which I resected. The osteomyelitis failed to heal after surgical intervention. Two subsequent surgeries resulted in a Chopart level amputation that successfully healed. I obtained appropriate shoes, inserts and a brace for the healed limb.
Two months after healing, a blister appeared on the plantar stump after he was barefoot in the shower. The wound became a full thickness ulcer and the patient subsequently received aggressive treatment with living skin equivalents and total contact casting, resulting in a healed wound once again six weeks later. I modified his insert and brace to accommodate the area of high pressure. Three months later, the wound opened again from minimal transfers to and from bed without his shoe. Again, I used an aggressive approach and achieved wound closure.
I offered the patient a surgical intervention to address the plantar prominent bones visible on radiographs but he refused. He received education on the high potential for wound recurrence, which ended up happening. A lengthy discussion with the patient, including his family members, determined the course of treatment. I advised the patient that wound healing was a possibility but keeping the wound healed did not seem realistic. Options included a proximal amputation versus palliative wound care.
After completely discussing the risks, complications, benefits and alternatives to these two options, the patient elected for palliative wound care. He was adamantly opposed to proximal amputation and accepted the risk associated with living with an open wound. He has been receiving palliative wound care every three weeks or prn in our clinic. For the past 18 months, he cleans and changes his dressing daily, applies hydrogel and wears a removable cast boot.
The second case involves a 60-year-old male veteran treated in a community outpatient wound clinic for a chronic great toe wound. His past medical history includes diabetes mellitus, hepatitis, peripheral neuropathy, a history of illicit drug use and active tobacco use of two cigarette packs per day. Attempts at healing the wound with eight applications of living skin equivalents and offloading in the outpatient setting were unsuccessful.
He presented to the ER with gas gangrene of the first ray. He immediately went to the OR for a partial first ray amputation with wide debridement resulting in a 17 cm x 5 cm open wound to the medial foot. After eliminating the infection, the patient’s options included conversion to a transmetatarsal amputation (TMA) with closure versus wound care in an attempt to heal the wound. After understanding the risks, benefits, complications and alternatives to each option, he chose wound care. He received aggressive porcine small intestinal submucosa, negative pressure wound therapy (NPWT), hyperbaric oxygen treatment (HBOT) and remained hospitalized in the extended care unit for four months. The wound became stable enough so we could manage the patient on an outpatient basis and continued advanced care reduced the wound size to 1.5 cm x 0.8 cm.
The patient once again presented with gas gangrene originating from the unhealed wound. Seven months after the initial infection, the TMA that I offered to him happened out of necessity. He was once again admitted and had an open TMA followed by delayed primary closure. There was dehiscence with the lateral TMA incision. The patient subsequently received living skin equivalents and NPWT, and ultimately healed during an 11-month process.
Despite being repeatedly advised about smoking cessation, the patient failed to quit smoking, stating “My smoking has nothing to do with the healing.” Additionally, while awaiting custom shoes that had been molded and were pending fabrication, he got explicit instructions to remain in the removable cast boot. However, he presented for a follow-up visit in athletic shoes with a sock wadded up in the forefoot of the shoe.
When questioned in the clinic, he stated, “I just wanted to wear a regular shoe. It isn’t going to be a problem.” He obviously continued to wear the inappropriate shoe and a lateral TMA wound developed. At this point, I referred the patient to orthopedics for a proximal amputation.
Dr. Rothenberg is the Director of Resident Training and an attending podiatrist in the Miami VA Healthcare System.
1. Sheehan P, Jones P, Caselli A, et al. Percent change in wound area of diabetic foot ulcers over a 4-week period is a robust predictor of complete healing in a 12-week prospective trial. Diabetes Care. 2003; 26(6):1879-1882.
2. Apelqvist J, Ragnarson-Tennvall G, Persson U, Larsson J. Diabetic foot ulcers in a multidisciplinary setting: an economic analysis of primary healing and healing with amputation. J Int Med. 1994; 235(5):463-471.
3. Product insert, Apligraf. Organogenesis, Canton, MA.
4. Product insert, Dermagraft. Shire Regenerative Medicine, La Jolla, CA.
5. Kimmel H, Regler J. An evidence based approach to treating diabetic foot ulcerations in a veteran population. J Diabetic Foot Complications. 2011; 3(3):50-54.
6. Tippett A. An introduction to palliative chronic wound care. Ostomy Wound Manage. 2012; 58(5):6-8.