What steps can one take to treat a wound that has not responded after a certain period of treatment? Our expert panelists discuss guidelines for assessing the efficacy of standard therapy, keys to addressing nutrition deficiencies and considerations for modifying the treatment regimen.
Q: What is the timeline to modify the wound treatment when the wound is not healing as you hoped?
A: All three panelists cite Sheehan’s study of diabetic foot wounds. The study notes that if the size of a wound does not decrease by 50 percent in four weeks, the wound has a 91 percent chance of not healing in 12 weeks.1
Lee C. Rogers, DPM, will attempt standard wound care for four weeks. He says standard care includes ruling out infection and vascular complications, ensuring proper offloading, performing weekly debridements and facilitating a moist healing environment. Dr. Rogers will change the treatment plan if the wound does not decrease by 50 percent in four weeks. 
Similarly, if Kazu Suzuki, DPM, CWS, does not see robust healing in three to four weeks, he will rethink his diagnosis and revise the patient’s treatment if necessary. At that point, he also considers advanced modalities such as negative pressure wound therapy (NPWT), skin substitutes and hyperbaric oxygen therapy.
If Dr. Rogers is in the midst of utilizing an advanced therapy like Dermagraft (Advanced Biohealing) and the wound “stalls,” he will stop Dermagraft, perform further debridement of the wound and then resume the interrupted therapy.
Guy Pupp, DPM, has been using the four-week timeline for years. In addition to Sheehan’s study, he cites a meta-analysis by Margolis and colleagues, who evaluated the rate of neuropathic ulcer healing in 10 control groups from clinical trials.2 Dr. Pupp also notes that the American Diabetes Association has concurred that a wound which remains unhealed after four weeks of standard treatment is a cause for concern due to the potential for worse outcomes.3
Q: Do you prescribe any nutritional supplements for wound healing?
A: Dr. Pupp believes patients with poor dietary habits, diabetes, infections and those undergoing dialysis should take nutritional supplements. A patient suffering from poor nutritional status will have a serum albumin below 3 g/dL, a total lymphocyte count below 1,500 cells per mm3 and poor dietary intake, according to Dr. Pupp. Drs. Suzuki and Rogers also advocate checking albumin, pre-albumin and lymphocyte counts.
As far as supplements go, Dr. Pupp notes that Metanx (PamLab) is formally indicated for the nutritional requirements of patients with endothelial dysfunction and/or hyperhomocysteinemia who present with lower extremity ulcerations. Dr. Pupp says physicians can also prescribe Metanx in order to address nutritional issues in patients with endothelial dysfunction who present with loss of protective sensation and neuropathic pain associated with diabetic peripheral neuropathy.
Furthermore, Dr. Pupp notes that deficiencies in arginine can cause poor wound healing. He says arginine triggers the body to make protein and also changes into nitric oxide, which causes blood vessels to dilate.
In regard to vitamins, Dr. Pupp says they can play a key role in facilitating wound healing.
Vitamin E preserves macrophages and polynuclear leukocytes, points out Dr. Pupp. If a vitamin E deficiency exists, Dr. Pupp says there may be impairment of wound healing. He says vitamin C is essential in the formation of collagen and notes that deficiencies can cause weakening and dehiscence of wounds. Dr. Pupp adds that Vitamin A is important for cellular differentiation and proliferation.
Vitamin D is necessary for strong bone healing and normal calcium metabolism, notes Dr. Pupp. He says vitamin B complex is a co-factor in many enzyme systems, collagen strength, protein synthesis and enhanced immune response. Iron is necessary for oxygen transport, collagen transport and is a constituent of hemoglobin, according to Dr. Pupp. He also notes that zinc assists with collagen synthesis, transport of vitamin A and enhancement of the immune response.
Although some nutritionists and nurses like to recommend zinc and vitamin C supplements, Dr. Suzuki notes insufficient clinical evidence.4
“I would rather not make my patients take extra pills although I would not make them stop if they want to take multivitamins,” maintains Dr. Suzuki.
Dr. Suzuki does advocate that patients eat as much protein as they can consume comfortably. He will tell patients to drink a few bottles of protein shakes a day. In his clinical experience, Dr. Suzuki has found that it is easier for patients to consume protein in liquid rather than solid form (i.e. chicken breasts). He suggests eating 1 g of protein per 1 kg of the patient’s ideal body weight as a general guideline.
If wound healing is impaired and nutritional deficit is thought to play a role, Dr. Rogers directs non-diabetic patients to drink one can of Ensure with meals and tells patients with diabetes to drink Glucerna. Dr. Rogers and colleagues are also in the midst of an ongoing randomized controlled trial investigating the supplement Juven (Abbott Laboratories) for wound healing.
Alternatively, Dr. Suzuki conducts a through interview of the patients and their families so he can obtain a general idea of how “well nourished” patients are in terms of protein intake. He cautions that obesity does not signify that patients have adequate albumin in their systems. If obese people become acutely ill, he notes they can still be large and malnourished at the same time.
“There is a difference between ‘well fed’ and ‘well nourished,’” says Dr. Suzuki. “Many studies have proved that ‘malnourished’ patients have more post-op complications and longer hospital stays versus ‘well nourished’ patients.”
Q: What do you try when the wound seems to be stuck and not progressing to healing?
A: First, Dr. Rogers will reevaluate the patient’s vascular status and offloading as well as check for infection. He will then consider growth factors, bioengineered tissue and/or curative surgeries. He notes a thorough, wide debridement can be necessary to jump-start the healing process.
Dr. Suzuki concurs with the importance of performing thorough sharp debridement as the first step to facilitating good wound healing. He also cites the Qoustic (Arobella Medical) low-frequency ultrasound debridement device, which he says can stimulate chronic and “stunned” wounds to get “unstuck.”
Dr. Pupp considers adjunctive measures if wounds do not respond in four weeks. He uses bioengineered skin substitutes including Apligraf (Organogenesis) and Dermagraft as well as autologous platelet growth factors.
“Although these modalities are expensive, their use can prevent extended costly wound care and help save limbs and lives,” maintains Dr. Pupp.
Dr. Suzuki finds it helpful to switch the wound dressings. In his experience, the most expensive dressing does not necessarily work the best since each wound has a different etiology and characteristics. For example, he notes if the wound is too wet or too dry, the wound healing will not progress.
“Changing the dressing materials, from say foam to alginate, or even from one brand to another, can possibly make a huge difference,” points out Dr. Suzuki.
In addition, Dr. Suzuki cites the importance of controlling edema. As he learned in residency training, an edematous limb is like a “flooded house.” Basically nothing works as it should and the body will not repair itself until the edema resolves, notes Dr. Suzuki. In addition to employing different kinds of compression bandages, hoses and leg pumps, he cites the importance of providing patient education and instructions to control leg edema.
Dr. Pupp is a Fellow of the American College of Foot and Ankle Surgeons. He is the Director of the Foot and Ankle Clinic at Oakland Regional Hospital in Southfield, Mich. He is also a member of the Residency Training Committee at Providence Hospital in Southfield, Mich.
Dr. Rogers is the Director of the Amputation Prevention Center at Broadlawns Medical Center in Des Moines, Iowa. He directs research at the center and has been an investigator on over 20 clinical trials.
Dr. Suzuki is the Medical Director of Tower Wound Care Center 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 of Tokyo Medical and Dental University in Tokyo, Japan. One can contact the author at firstname.lastname@example.org .
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1. Sheehan P, Jones P, Giurini JM, Caselli A, 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. Plast Reconstr Surg 2006 Jun; 117(7 Suppl):239S-244S.
2. Margolis DJ, Kantor J, Berlin JA. Healing of diabetic neuropathic foot ulcers receiving standard treatment. A meta-analysis. Diabetes Care 1999 May; 22(5):692-5.
3. American Diabetes Association. Consensus development conference on diabetic foot wound care, 7-8 April 1999, Boston, MA. Adv Wound Care 1999 Sep; 12(7):353-61.
4. Cochrane Database of Systematic Reviews 2008, Issue 4. Art. No.: CD001273. DOI: 10.1002/14651858.CD001273.