When To Turn To Advanced Therapies For Wounds

At what point should physicians seek advanced therapies for chronic wounds? These expert panelists discuss the guidelines for starting advanced therapy and which therapies show promise.  

Q:

What kind of advanced therapies for wounds do you use, beyond conventional wound debridement, moist dressing, offloading and compression?

A:

In his wound clinic, Kazu Suzuki, DPM, CWS, and his colleagues often rely on various skin substitute grafts. He believes skin substitutes are “the biggest game changer” in wound care when it comes to closing hard to heal wounds.

Dr. Suzuki uses negative pressure wound therapy (NPWT) devices such as Vacuum Assisted Closure (VAC, Acelity) often but perhaps not as often as five years ago because of his success with skin substitute grafts. Stephanie Wu, DPM, MSc, FACFAS, Andrew Rice, DPM, FACFAS, and Robert Snyder, DPM, CWS, also cite the efficacy of NPWT. In hospitalized patients and for outpatients with deep or complicated wounds, Dr. Rice uses NPWT as a first-line treatment. Dr. Snyder says NPWT, instillation therapy, epidermal blister grafts and matrices from other sources (i.e. equine, submucosa) may be “extremely important” adjunctive treatments to standard of care algorithms.

Dr. Wu notes the advanced therapies she utilizes for wounds consist of various bioengineered alternative tissue products such as acellular dermal matrices and amniotic membrane allografts. She also uses epidermal skin grafts, split-thickness skin grafts (STSGs) and skin flaps.

After preparing the wound, Dr. Snyder notes various evidenced-based dermal matrix products can accelerate healing of chronic/stalled wounds. These range from homologous use products such as amniotic membranes to collagen matrices and living skin equivalents. When appropriate, he notes STSGs and flaps remain “essential elements of the reconstructive ladder.” For hospitalized patients, Dr. Suzuki often performs wound debridement in the OR along with STSG, skin flaps and muscle flaps, often in conjunction with NPWT or instillation NPWT, which is effective in controlling severe infection.

Dr. Snyder notes it is essential to follow the wound bed preparation model—debridement, control of infection/inflammation, moisture control and wound edge preparation—especially when readying the area to accept an advanced product. He cites advanced wound products including collagens and collagen/oxidized regenerated cellulose (ORC) to lower protease activity, various antiseptics (i.e. silver, cadexomer iodine, and polyhexamethylene biguanide) to address increased bioburden, and topical agents to disrupt biofilm activity.

Dr. Rice also cites the use of debridement agents, such as Microcyn (Sonoma Pharmaceuticals) and Santyl (Smith and Nephew), to reduce bioburden/biofilm. As the wounds progress and are “clean,” Dr. Rice says one can promote granulation tissue with biologic products such as Regranex (Smith and Nephew), Stravix (Osiris Therapeutics), Neox (Amniox Medical) or biologic matrix scaffolds such as cryopreserved human dermis and Integra Bilayer Matrix Wound Dressing (Integra LifeSciences).

“Fortunately, we practice at a time when multiple products and devices are available for complex wound treatment,” says Dr. Rice.

Dr. Suzuki does use hyperbaric oxygen therapy (HBOT) for severe diabetic foot ulcers that need extra help in wound healing or when limb preservation is at stake. Radiation wounds (often seen in the treatment of those with lower extremity skin cancers) also get an automatic referral for HBOT in Dr. Suzuki’s clinic. He notes radiation wounds are extremely hard to heal and, in his opinion, HBOT is the only medical treatment that reverses soft tissue radionecrosis.

Q:

What guidelines do you use to determine when to use advanced therapies for wounds?

A:

Dr. Wu cites the commonly used criteria in deciding the need for an advanced therapy: the percent change in ulcer area after four weeks of good wound care.¹ As she notes, this tool has been widely adapted as a pivotal clinical decision point for identifying patients who may not respond to standard wound care.  

As Dr. Snyder explains, the study by Sheehan and colleagues advocates that if a foot ulcer in a patient with diabetes fails to have a 50 percent area reduction in the first four weeks, it is a negative predictor of healing by week 12.¹ However, he notes that even in patients who reach this threshold, almost 50 percent will fail to heal within that timeframe. Within the next eight weeks, wounds that plateau at weeks four to six or fail to progress by 90 percent at week eight will not heal by week 12, according to Dr. Snyder. He says this should alert the clinician as to when an advanced product may be beneficial.

Dr. Snyder also notes that the WIfI classification (i.e. wound, ischemia, infection) is helpful in determining if a patient would benefit from vascular intervention and in determining the likelihood of amputation.²

Dr. Suzuki advocates assessing the patient’s overall medical condition and potential wound healing abilities. If he suspects any factors that may delay wound healing, Dr. Suzuki will utilize advanced wound therapies. Red flags that he says indicate slow or suboptimal wound healing include age over 80, dialysis or poor appetite. Based on his experience and research, Dr. Suzuki says patients with diabetes will not heal very fast due to poor collagen deposition, inadequate blood glucose control, challenges with offloading and many other factors.³ He also sees patients on chemotherapy or post-radiation therapies, and says they are just as challenging as patients with diabetic wounds if not more so.

In deciding when to use advanced products, Dr. Rice follows his and his colleagues’ experience. When it comes to promoting granulation tissue with deep or complicated wounds, he uses NPWT or negative pressure with an amniotic tissue allograft. For plantar wounds, he often uses a fenestrated wound scaffold with human dermis, using the Integra allograft and NPWT first, and then applying STSG or repeating amniotic allograft use. To promote the epithelial tissue, Dr. Rice has used Cellutome (Acelity) in stalled wounds with a granulation bed.

Q:

Are there any newer advanced therapies that you find effective or promising?

A:

Dr. Suzuki mentions Kerecis Omega3 (Kerecis), a fish-based skin substitute graft. He says this graft has a potential to be inexpensive and has the advantage of not being sourced from human or mammalian donors, meaning there are no concerns for transmission of most diseases because of cross-species implantation of skin or skin-like materials.  

“I believe skin substitute grafts have dramatically improved our wound healing rate without resorting to more complex surgical procedures, such as skin flaps and skin grafting,” says Dr. Suzuki.

Drs. Suzuki and Snyder also have used instillation NPWT. Although its indication is limited to acute care and those with severely infected wounds, he says NPWT instillation significantly hastens wound closure and decreases the length of stay in the hospital.

Dr. Wu notes that cellular therapy and bioengineered autogenic-allogenic hybrid products have shown promise in preclinical research. She cautions that randomized clinical trials will be needed to better assess their efficacy.

“While the newer advanced therapies have demonstrated some clinical efficacy, there has yet to be an ultimate end-all, be-all product that heals all wounds,” asserts Dr. Wu.   

For four or five years, Dr. Rice has used amniotic tissue therapies and says they appear to be promising. In his clinical experience, amniotic tissues promote tissue healing faster with reduced rates of infection relapse.

Dr. Snyder points to new wound therapies such as epidermal blister grafts, fluorescence angiography and topical agents that disrupt biofilm. He also cites the use of point-of-care diagnostic tests (such as those for proteases and infection) as well as polymerase chain reaction DNA analysis of bacteria and biofilm.

Q:

Are there any drawbacks or contraindications to advanced therapies?  

A:

The presence of poor vascularity, uncontrolled diabetes and infection present potential contraindications for using adjunctive interventions, according to Dr. Snyder. Dr. Rice also cites ischemia as a contraindication.
Dr. Wu says patients generally tolerate most advanced therapies well. She adds that each product may have specific contraindications, such as an allergy to one of the components or preservatives.  

Dr. Wu emphasizes that one should ensure the basic components for wound healing are adequate and well controlled prior to utilizing advanced therapies. Neglecting to do so can often lead to the failure or decreased efficacy of advanced therapies, according to Dr. Wu. She notes factors to watch include debridement, vascularity, bioburden, offloading for plantar diabetic foot ulcers and compression for venous leg ulcers. Dr. Snyder agrees, emphasizing that one must prepare the wound appropriately before contemplating an advanced product. Prior to application, he says it is essential to obtain a complete history and physical.

The biggest drawbacks of advanced therapies, notes Dr. Suzuki, are cost and insurance coverage. As he notes, all of the newer therapies do not have a generic equivalent and some skin substitute grafts (especially the human cell-based products) can be fairly expensive without adequate insurance coverage.

Dr. Rice is an Assistant Clinical Professor in the Department of Orthopedics and Rehabilitation at the Yale University School of Medicine. He is in private practice at Fairfield County Foot Surgeons in Norwalk, Conn. He is a Fellow of the American College of Foot and Ankle Surgeons.

Dr. Snyder is a Professor and the Director of Clinical Research at the Barry University School of Podiatric Medicine. He is also the Director of the Fellowship Program in Wound Healing and Clinical Research at Barry University. Dr. Snyder is a Past President of the Association for the Advancement of Wound Care and the American Board of Wound Management.

Dr. Suzuki is the Medical Director of the Tower Wound Care Centers at the Cedars-Sinai Medical Towers. He is also on the medical staff of the Cedars-Sinai Medical Center in Los Angeles and is a Visiting Professor at the Tokyo Medical and Dental University in Tokyo. He can be reached at Kazu.Suzuki@cshs.org.

Dr. Wu is the Associate Dean of Research, and a Professor of Surgery at the Dr. William M. Scholl College of Podiatric Medicine and a Professor of Stem Cell and Regenerative Medicine at the School of Graduate Medical Sciences at the Rosalind Franklin University of Medicine and Science. She is also the Director of the Center for Lower Extremity Ambulatory Research (CLEAR) in Chicago.

References

1. Sheehan P, Jones P, Caselli A, Giurini JM, Veves A. 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):1879-82.
2. Mills JL, Conte MS, Armstrong DG, et al. The Society for Vascular Surgery Lower Extremity Threatened Limb Classification System: Risk stratification based on Wound, Ischemia, and foot Infection (WIfI). J Vasc Surg. 2014;59(1):220034.e1-2.
3. Suzuki K, Birnbaum Z. Skin perfusion pressure and wound closure time in lower extremity wounds. Symposium on Advanced Wound Care (SAWC) Spring 2017 poster presentation. Adv Skin Wound Care. In press, 2017.