February 2009

This letter is in reference to Williams RL. Cadexomer Iodine: An Effective Palliative Dressing in Chronic Critical Limb Ischemia. WOUNDS. 2009;21(1):15–28.

Studies performed on a limited number of demographically similar patients without a control arm or randomization may still provide useful clinical information when the results are carefully reviewed, scrutinized, and presented in an objective fashion.

One of the conclusions drawn from this limited number of patients (n = 11) is that “cadexomer iodine is an effective palliative dressing for wounds with CCLI.” Without a valid number of patients and an acceptable control, statements on autolytic debridement, anti-inflammatory effects, and the promotion of wound closure through granulation and epithelialization are, at best, assumptions. The author should also take care in making statements that the cadexomer iodine facilitates dry gangrene, a process that I would not want to see promoted by any product. I believe the intent was to state that the product promotes demarcation of viable from nonviable tissue although, even this assumption needs further investigation.

The limited number of patients reviewed is not as great a concern as the subjective conclusions and theories presented. The rationale for “cautious debridement” is justified,¹ but does not support the conclusion that amputations that are delayed, may significantly improve quality of life for the affected individual. References are cited for the beneficial effects of decreasing bacteria and incidence of infection in ischemic wounds, however the data referenced is based on wounds associated with presumably acceptable blood flow. Data on the possibility of introducing infection and contributing to amputation through debridement would be desired in such a paper. I agree that while true gangrene or putrification of tissue may contribute to amputation and sepsis, the difference between a true gangrene and dry gangrene needs to be clarified both in appearance and definition. The term “dry gangrene” often is used to describe dry eschar on a wound surface, a material that is anything but putrifying.² Evidence is needed to support the presence of high levels of bacteria in dry gangrene that may lead to bacterial dissemination, infection, and possible sepsis. There is also no evidence currently available that indicates dry eschar or dry necrotic tissue mitigates the inflammatory process. Neither is evidence available supporting conservative debridement as a means of preventing further gangrene or progressive infection.

The belief that preventing amputation will lead to a better quality of life is concerning. Implying that a limb with wounds and even osteomyelitis might allow for better function ignores the vast improvements made in prosthetics, which allow for excellent function and ambulation, thus improving the individual’s quality of life. Small areas of necrosis, such as dry necrosis of the digits, may be adequately addressed through self-amputation versus surgical intervention. Patients who are poor surgical candidates may suffer greater morbidity or mortality from a surgical intervention. When more extensive necrosis is present, numerous factors must be considered, particularly the existing quality of life. No information is presented on what the patient’s quality of life or mental status was during the conservative treatment period, nor is the eligibility of each patient for a surgical procedure discussed in detail.

In many instances, a below knee amputation may allow for rapid ambulation, decreased pain, and a return to an almost normal lifestyle while deferring amputation and keeping a patient non-weightbearing, which may decrease quality of life and prevent ambulation. Many unsupported assumptions that are presented may mislead readers into believing that it is best to delay amputations as long as possible. In cases where amputation is inevitable, as appears to be the case with some of the cohort patients, a thorough review of the patient’s medical status, medical history, and lifestyle should be considered before deciding whether conservative or surgical approaches are appropriate. Patients who are better served by amputation may require extensive patient and family education as well as counseling to assist with their final decision to proceed with amputation.

Additional treatment modalities, including the circulator boot, are mentioned and a detailed explanation of how these products may assist with wound closure associated with marginal blood flow is warranted. A brief review and discussion of additional adjunctive modalities including hydro-debridement, hyperbaric oxygen, and other devices assisting arterial flow, would provide an objective overview of the various conservative options available for patient care.

The topic of conservative debridement and deferment of amputations is welcomed in the medical literature, particularly in a society prone to amputating as a primary approach to treating the lower extremity with ischemic lesions. However, the topic should be presented in a balanced and scientific manner, avoiding trite terminology, exaggerated statements, and unsubstantiated assumptions. Rationale for choosing a conservative versus a surgical approach, the advantages and disadvantages of each choice, as well as indications and contraindications for each approach, are inadequately discussed in this manuscript.

Even when conservative debridement and care is in the individual’s best interest, clear algorithms and guidelines with supporting references would help both the clinician and patient in their treatment choice.

Gerit Mulder, DPM, MS
Director of Wound Treatment and Research Center
Professor of Surgery and Orthopedics
Department of Surgery/Division of Trauma
University of California San Diego

References
1. Barbul A. Wound Care Guidelines of the Wound Healing Society. Wound Repair Regen. 2006;14(6):645–711.

2. WordNet: A Lexical Database for the English Language. Dry gangrene. Available at: https://wordnetweb.princeton.edu/perl/webwn.
 

Dear Editor:

Many of Dr. Mulder’s criticisms of the article (Cadexomer Iodine: An Effective Palliative Dressing in Chronic Critical Limb Ischemia) are valid and much appreciated.

The sample size was extremely small, and the article should not be used to draw any definitive conclusions about the management of wounds associated with critical limb ischemia. The gold standard for a basis of such sweeping conclusions would require a prospective, multicenter, randomized, double-blind, controlled study involving thousands of patients. Ultimately, it would be ideal if the resources, practitioners, and patients could be obtained and organized to answer the question posed by Dr. Mulder: How can wounds associated with chronic critical limb ischemia be consistently and definitively cured? The field is longing for “clear algorithms and guidelines with supporting references” to facilitate treatment decisions. Unfortunately, financial support of such an undertaking has not yet been amassed.

To clarify my simple-minded distinction of wet and dry gangrene, I will explain that I apply the term “gangrene” to limbs or digits that appear to consist of mostly dead and nonviable tissue rather than just superficial eschar. If the necrotic tissue is moist and draining, and if the surrounding viable tissue is inflamed, I tend to consider this “wet gangrene.” If the necrotic tissue is dry and there is readily identifiable demarcation between viable and nonviable tissue with little to no inflammation involving the viable tissue apparent, I tend to consider this “dry gangrene.” If this state of dry gangrene persists long enough and if infection does not ensue, the process of autoamputation may proceed naturally without any intervention. Occasionally, when surgeons fear that surgical intervention is likely to cause more harm than good, they may recommend attempting autoamputation.

That cadexomer iodine might facilitate dry gangrene was based on its antimicrobial and drying properties, and served as the basis for testing it as a palliative dressing in patients refusing amputation. Our experiences in this small cohort, as presented in the article, demonstrated the success we had using the product to prevent dry gangrene converting to wet gangrene. Scientific proof of this hypothesis can only be proven prospectively with controls.

The statements on autolytic debridement, anti-inflammatory effect, and promotion of wound closure through granulation and epithelialization associated with cadexomer iodine were not assumptions but were anecdotal observations made while treating these patients. The photos included in the article were selected so that the reader might be able to appreciate these observations rather than merely taking the author’s word. It is also noteworthy to mention that these observations were appreciated in our treatment of many other patients seen in our facility that did not meet the criteria to be included in this particular article. The value of all these observations, no matter how many patients, is only anecdotal, but this is an inherent limitation of a retrospective cohort study. These observations are, however, consistent with information available elsewhere in literature, which was sited in the article, and are also consistent with material produced by the product’s manufacturer.

I am also grateful that Dr. Mulder noted the reference to “cautious debridement.” It is my opinion that care must be taken to gently remove old dressing material and some necrotic tissue, taking care not to elicit an inflammatory reaction. If one continually applies the dressing material allowing it to build up by continually applying additional layers of the product, they may not see the same results we have seen. On the other hand, it is well known that aggressive debridement of ischemic wounds elicits an inflammatory reaction that precipitates rapid wound bed deterioration. Though not yet proven scientifically, I believe gentle and cautious debridement is a critical step necessary for optimizing outcome when using this product.

The patients presented in the article were selected to fit specific criteria of having critical limb ischemia and were patients for whom amputation had legitimately been considered. Decisions not to amputate were not based on expectations of the healing effects of cadexomer iodine, but rather these were patients who either refused amputation or were believed to be such poor surgical candidates that it was feared they would either not survive surgery or was not likely be able to ambulate following surgery despite the wonderful advances made thus far in prosthetics. Although the article touched on the sensitive and spiritual nature of physicians and patients deciding on palliative therapy in lieu of aggressive medical interventions, it was not the intent of this article to define that process.

It should be emphasized that the purpose of this paper was to introduce cadexomer iodine as a means of stabilizing wounds associated with critical limb ischemia while definitive measures addressing ischemia such as bypass surgery, percutaneous angioplasty, or noninvasive measures, such as intermittent compression therapy, could be implemented.

Using the dressing palliatively without addressing the underlying ischemia would only be appropriate if the patient refused or was not a candidate for any reperfusion interventions. When cadexomer iodine was used for a purely palliative intent in our clinic, it was always clearly communicated to the patient that cure was not expected and that the dressing would at best potentially delay the inevitable need for amputation. Patients with such advanced disease and numerous serious comorbid diseases who were not candidates for successful revascularization and were also not good surgical candidates for amputation did appear to benefit from end-of-life care that did not include amputation. This is, however, a subjective conclusion drawn from personal communication with these patients and their families.

Whether proceeding with revascularization measures or abandoning aggressive intervention for palliative end of life therapy, cadexomer iodine has served us well in optimizing the care of ischemic lower limb wounds. I hope the article successfully communicated to wound care specialists the value of this product in tailoring an individualized treatment plan for each patient seeking relief from this class of wounds.

Robert Williams, MD
Huntsville, Texas

Dear Editor:

I appreciated Dr. Laura Bolton’s treatise on honey (Evidence Corner. Topical Honey and Wounds. 2008;20[Dec]:A13–14). I can still recall a medical school professor who, nearly 30 years ago, commanded me to treat a woman’s infected open chest by squirting honey directly from the Sue Bee bottle onto her beating mediastinum on a daily basis. Then there was the surgery chief who pulled a wad of Doublemint gum from his mouth and stuffed it in an enterocutaneous fistula during rounds. I suppose nothing is new.

Dr. Bolton’s reference from the Cochrane database that described using 70% ethanol on wounds (egads!) caused me to pause. I did a study with Edward Falces, MD (San Francisco, CA) wherein we plotted increasing concentrations of sodium hypochlorite versus decreasing bacterial survival versus decreasing fibroblast survival. There is a unique concentration and pH (and it is not Dakin’s concentration) at which maximum bactericidal activity and minimal fibroblasticidal activity occurs. Sorry to say, too many practitioners are blinded by the bactericidal activity of topicals and ignore the toxic effect on fibroblasts. We see this with the abuse of iodine and peroxide on wounds.

"If a little is good, surely more has to be better?” What have you gained if you have a sterile wound that won’t heal?

John Baeke, MD
Park Place Plastic Surgery
Overland Park, KS