Healing impairment in chronic diabetic wounds is related to many biologic processes, but a salient factor is the insufficiency of the human immune system to combat bacterial contamination.1,2 Chronic insulin-dependent diabetes creates vascular disease through molecular changes, deposition of glycation products that stiffen vessels via increased basement membrane permeability, and disrupting basic wound healing processes.3 Vascular resistance is increased by alteration of vessel diameter, which leads to enhanced tissue ischemia and microvascular sludging at the capillary level. The combined effects of these disorders make patients with other comorbidities fragile and susceptible to infection, amputation, and delayed wound healing.4,5 Older adults may have malnutrition, cardiovascular disease, and chronic dementia, which add to the risk profile.
This case report considers two such older adults where healing had stalled with standard wound treatments, and the patients were debilitated to the extent that reconstructive surgical procedures were out of the question. From the wound healing literature consensus, the TIME (tissue, infection/inflammation, moisture balance, and edge of wound) paradigm is an important consideration for implementing treatment. The author introduced the Charlson comorbidity index (CCI) to risk stratify the patients in this study. The CCI was introduced in 1987 by Mary Charlson, MD,6,7 for assessing the effect of chronic disease in patients with cancer by determining 1-year mortality in this setting. Significantly, both cases had a very high CCI, indicating severe chronic underlying disease burden. The other remarkable finding was the efficacy of frequent daily saline irrigations to stabilize both wounds to healthy-appearing granulation tissue. Several attempts were made to accomplish the TIME step-down method only to have necrosis and chronic inflammation return.
This study was sponsored by the author and approved for clinical investigation by the Sterling Investigational Review Board, Atlanta, Georgia (#6606-001). The study used an uncontrolled open-label design, and there were no exclusions to treatment. The study involved high-risk patients for whom treatments had not been successful for a minimum of 3 months. Fourteen patients consented and were treated to assess the safety and efficacy of pressurized jet lavage irrigation for treating problems where wound healing had stalled. For this cohort, the average CCI was 7.6 (CCIs >5 are considered severe).6,7
Two patients who had treatment extended beyond 26 weeks to a treatment endpoint are the subject of this case report. These patients were of specific interest because of severe diabetic vascular disease, unilateral below-knee amputation, stalled wound healing and chronic wounds that had not responded to 4months’ standard treatment. Both patients provided permission to publish the case details and associated images.
A 65-year-old man was evaluated for treatment of a stage 4 175-cm2 pressure injury with severe tunneling and exposed bone (Figure 1A). He was 6 months postoperation for an intertrochanteric hip fracture of his right leg that had previously undergone a below-the-knee amputation for severe diabetic foot pressure injury. He also had a Wagner stage 3 open pressure injury exposing the metatarsal phalangeal joint of his opposite leg hallux. His comorbidities included stroke, brittle insulin-dependent diabetes, coronary artery disease, peripheral vascular disease, and chronic dementia. His CCI was 10. His serum lymphocyte count was 800 cells/mcL, (normal, >1,500 cells/mcL), and his prealbumin level was 8 mg/dL (normal, >16 mg/dL), indicating infection inflammation and probable increased disease burden.8,9 The sacral pressure injury developed on his right leg during a 2-week hospitalization for the hip fracture, and he had been discharged from the hospital with negative-pressure wound therapy (NPWT) and daily application of a collagenase for the pressure injury on the sacrum.
After 4 months of treatment, healing of the pressure injury had stalled, and the wound had a gray, smooth appearance without the expected red granulating surface. He had two recent hospitalizations for systemic sepsis managed with IV antibiotics. The negative pressure was difficult to maintain, and the pad was close enough to the anus that the wound bed was often contaminated with feces. The wound produced a large amount of daily slough and extraordinary odor. The treating primary care physician agreed to alternative treatment, and the patient was consented for this study.
Daily treatment was initiated with a handheld pulsatile irrigator delivering 3 L of saline to the wound under “low pressure” (<15 pounds per square inch).10,11 Treatment was done at the bedside by physical therapists, and effluent was collected in a novel fluid collection bag designed to cover the sacral wound, creating a watertight seal with a wide margin of double-film ostomy tape (Figure 1B). Following the recommendations of several prior authors, treatment included irrigation 5 days per week in the outpatient setting.12–18 To address the wound tunneling, providers used a special long irrigator tip initially designed for femoral canal irrigation in total hip replacements. They also treated the left foot pressure injury with the exposed metatarsal phalangeal joint with 3 L of saline delivered under low-pressure jet lavage irrigation and used a fluid collection bag designed to cover extremity wounds.
Within 10 days, both wounds showed much lower amounts of slough and no odor. Early bedside sharp debridement without anesthetic was required on several occasions for the sacral wound, causing a modest amount of bleeding.19 The sacral wound was “wet” for the first 10 days, but once granulation tissue was apparent, all minor capillary blood oozing ceased and never recurred. It was later recognized that the patient was on maintenance anticoagulant treatment for his stroke history, peripheral vascular disease, and coronary artery disease. This factor did not cause a complication.
After 5 months of treatment, there was substantial improvement with the sacral wound down to about 60 cm2 and complete resolution of the tunneling (Figure 1C). The sacral wound demonstrated excellent healthy granulation and had no odor, and the patient had no further episodes of systemic sepsis. Reducing irrigation to 3 days per week caused the wound to lose its healthy appearance, so daily jet lavage wound irrigation was resumed.
One month later, the patient had an upper respiratory tract infection that progressed to pneumonia. He returned to the nursing home and resumed treatment with NPWT and collagenase applied to the sacral wound. Within 7days, the wound surface was turning gray, and several small necrotic spots began to appear (Figure 1D). Daily jet lavage irrigation was reinstituted, and the necrosis quickly resolved within a week. This exercise was repeated a second time when the patient underwent amputation of the contralateral limb first metatarsal ray and a diverting colostomy (Figure 1E). The patient lived 4 more months with a healthy wound, with granulation tissue completely covering the previously exposed 1 area of sacral bone. The patient died of natural causes.
A 70-year-old woman was evaluated for treatment with a 35-cm2 heel pressure injury (Figure 2A). The wound had a dense scab covering 40% of its surface and a moderate amount of slough. The patient had been treated for nearly a year with NPWT and collagenase. The patient had insulin-dependent diabetes and severe peripheral vascular disease, with the contralateral leg amputated from an advanced necrotic foot ulcer. Other comorbidities included severe obstructive pulmonary disease and chronic dementia. Her CCI was 11. Daily jet lavage irrigation was instituted, and within 2 weeks, the fibrotic “black cap” disappeared, with the wound converting to a healthy appearance.
Careful pressure control of the heel and daily irrigation over the next several months significantly improved the wound. The patient had a wound healing relapse at 4 months following 5 days without treatment over a holiday season. Pressure injury may have been involved. The substantial decline in wound appearance quickly improved with daily irrigation. A month later, the patient was admitted with pneumonia and returned to the nursing home with NPWT with daily collagenase to the wound. Over the ensuing week, the wound developed several dark spots and lost the red color of healthy tissue granulation. Daily jet lavage irrigation quickly resolved the adverse outcomes. The wound was completely closed after 10 months of jet lavage irrigation, remaining healed over the next 4 months, after which the patient died (Figure 2B).
This case series reveals that there is a level of microvascular disturbance where typical wound treatment with cleansing, moisture management, and even NPWT is not adequate. Also, daily low-pressure irrigation can resolve inflammation and enable angiogenesis. Case 1 had been septic on several occasions requiring hospitalization. His wound was grossly contaminated daily by fecal material, and he eventually had a diverting colostomy. Case 2 had been advised to have a below-the-knee amputation as her wound had not responded to nearly a year of NPWT treatment. Neither patient experienced significant pain during the course of treatment, but case 1 had discomfort during the first few treatments; this was dealt with by using the low-power setting, which produced irrigation at 700 ccs/min versus standard irrigation at 1,200 ccs/min. Case 1 had 169 treatments over a 51-week period, and case 2 had 131 treatments over a 50-week period.
The use of daily jet lavage pulsatile irrigation was significantly less costly than a parallel approach with NPWT, because the method is a surgical procedure that offers a separate CPT code covered by Medicare Part B and Medicaid in the outpatient setting. For case 1, over a 10-month period, the cost was $18,600 for the kits, and the CMS Medicare Part B reimbursement for the kits was $19,225. Case 2 was treated over 12 months at a cost of $14,410 with a CMS Medicare Part B reimbursement of $11,176. The difference relates to the lower reimbursement of the 97597 code used to treat the heel ulcer compared with the 97598 code for the larger wound. The nursing home quoted their cost experience with NPWT systems as averaging $3,000 per month for nonreimbursed dressings. This translates to $30,000 direct costs to the nursing home for case 1 and $36,000 for case 2 that are not covered by a separate CMS code.
The other important consideration is the level of patient comorbidity. A recent hospital study demonstrated that risk factors that lead to lower extremity amputation in patients with diabetes included poor glycemic control, hypertension, hypertriglyceridemia, and infection.5 The CCI is a recognized tool for assessing the burden of chronic disease and was utilized by the author in all patients of the study cohort.6,7 The CCI has been upgraded several times in the medical literature with age adjustment and whittling down categories such as peripheral vascular disease where treatments have advanced. There are now a few wound literature citations where this method was a descriptive noncontinuous variable. The CCI or other such standard tools can help guide treatment. For chronic wound infections, blood plasma markers such as transthyretin may be a useful adjunct assessment. Prealbumin (transthyretin), which is produced primarily by the liver and has a baseline blood level of 16 mg/dL from our hospital laboratory, is commonly associated with chronic infection inflammation and malnutrition. C-reactive protein is produced by the liver in acute inflammation at the expense of prealbumin, which is depressed. Depressed prealbumin may be associated inversely with the CCI and is correlated with underlying disease burden.8,9
Selective mechanical debridement with low-pressure jet lavage irrigation has been well accepted as a method for treating contaminated and infected wounds.12–18 Pulsatile irrigation does not pose any known risks to outpatients. The Agency for Healthcare Policy and Research reviewed this technology, and the consensus panel set a ceiling pressure at 15 pounds per square inch. The FDA has determined that pulsatile irrigators must be single use and sterilized, but require no premarket approval as they are considered 510(k) exempt.10,11 The Cochrane Database meta-analysis review would suggest that evidence is generally positive for this method but limited in nature with very few high-evidence randomized controlled trials.20 That stated, the surgical profession has used this treatment widely for effective cleansing of acute wounds, treatment of infected wounds, and removal of biofilm bacteria in chronic wounds. Mechanical debridement with low-pressure jet lavage irrigation has been indicated as an effective wound bed preparation method prior to advanced treatments under the TIME wound management methodology.1,10,21 Most states allow midlevel providers such as physician’s assistants, NPs, and physical therapists by statute to independently perform outpatient low-pressure jet lavage therapy and advanced practice wound nurses to provide the treatment under direct physician supervision.
A key problem with wound healing is the biofilm/bacterial bioburden in chronic wounds. Bacteria are highly effective in controlling the local environment, with elevation of factors such as matrix metalloproteinases to extraordinary levels that diminish the ability of the human immune system to control the infection.2,22 Bjarnsholt et al2 hypothesized that to reverse this process, providers must remove bacteria and detrimental factors, such as matrix metalloproteinases, from the wound. The medical literature is clear that mechanical debridement is the optimal initial treatment method, but the recent TIME concepts of Schultz et al1 further advocate using a multimodal approach, such as optimizing overall diabetes care, removing risks of pressure, and optimizing the health of the host.1,21
For jet lavage, early wound bed preparation for biofilm control is a logical indication for usage. The goal of treatment is to get these wounds stable from the microbiologic viewpoint, that is, less than log 4 to 5 colony-forming units (CFUs)/g, and then resolve the inflammation issues.10 Alternative treatments could include other mechanical methods such as frequent local sharp debridement, monofilament sponge debrider (Debrisoft, Lohmann & Rauscher, Milwaukee, Wisconsin), low-intensity ultrasound, and typical antiseptic/surfactant solutions.10,23–25
During this study, the author’s treatment team consistently applied antiseptic solutions each day, and the author tried several, including Prontosan Gel (B. Braun Medical, Bethlehem, Pennsylvania), BlastX Gel (Next Science, Sydney, Australia), and Dakin solution 0.187% (Covenant Medical Services Inc, Maryland Heights, Missouri). A multimodal approach is critical in these cases, and topical antiseptics probably played a role in the outcome.10
This case report is unique because the TIME step-down approach allowed neither decrease nor discontinuation of the pulsatile irrigators. The human burden of failed or “stalled” treatment should not be minimized. Families of these patients did not want their relative to suffer from a painful wound or wound odor. Because this report comes from an institutional review board study, the families were carefully advised that the treatments, although experimental, were not ill-conceived and offered great potential benefit. They were pleased with what the study demonstrated.
Is there other medical evidence to support the added complexity of daily wound irrigation with a jet lavage procedure? Wolcott et al26 showed how easily bacteria return to infection-level contamination from baseline at greater than 1 × 105 CFUs/g of tissue by 72 hours after surgical debridement. Similarly, Yang et al27 demonstrated from a porcine skin model that even less virulent species of bacteria than those typically found in a human wound are able to repopulate the wound model to greater than 1× 105 CFUs/μL within 48 to 72 hours. Although the clinical situation may not directly mirror these experimental findings, high-risk problems, such as these two cases, are clearly going to behave poorly with standard treatments every 2 to 3 days.
This case report identified two cases where standard treatments were not effective for advancing wound healing in high-risk patients. Daily jet lavage pulsatile irrigation with 3 L of saline in the outpatient setting was successful in reversing this trend. Significantly, attempts to return to prior treatment or stepping down to less intense daily irrigation caused a recurrence of wound ischemia.
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