Abstract
In this study, we evaluated the utility of a dermal substitute for preserving maximal foot length after urgent surgical debridement. Patients referred to our Diabetic Foot Center with foot lesions were assessed for sensory–motor neuropathy, infection and critical limb ischaemia. The presence of acute foot infection indicated the need for immediate surgical debridement. The degree of amputation, if necessary, was based on the amount of apparently non infected vital tissue. When vital tendon/bone tissue remained exposed, the lesion was covered with a dermal substitute. From January to December 2008, 393 patients underwent surgical treatment for diabetic foot syndrome; 30 patients underwent immediate surgical debridement resulting in exposed tendon and/or bone tissues. An average of 4·4 ± 2·1 days following surgical debridement, all 30 patients underwent dermal regeneration template grafting to cover‐exposed healthy tendon and bone tissues, instead of achieving primary wound closure with a proximal amputation. After 21 days, a skin graft was performed. Complete wound healing occurred in 26 patients (86·7%). In these patients, the amputation level was significantly more distal (P < 0·003) with respect to that potentially required for immediate wound closure. The average healing time was 74·1 ± 28·9 days. Four patients underwent a more proximal amputation. No patients underwent major amputation. The use of the dermal substitute for treating exposed tendon and bone tissues allowed timely wound healing and preserved maximal foot length. Continued follow‐up will allow assessment of long‐term relapse and complication rates. Such treatment could constitute part of the comprehensive management of diabetic wounds.
Keywords: Dermal substitute, Diabetic foot infection, Foot length, Minor amputation
INTRODUCTION
Improvements in diagnostic and therapeutic techniques and the adoption of multidisciplinary approaches for managing diabetic foot disease have enhanced limb salvage rates 1, 2. Treatment of feet presenting with infection or widespread gangrene consists of surgical removal of the infected soft and non vital bone tissues, often leading to minor amputation even at proximal levels (i.e. Chopart amputation). Following aggressive debridement, a lack of soft tissue available for covering exposed bones and healthy tendons may necessitate more proximal amputation to achieve immediate surgical wound closure, resulting in shortening of the foot stump. Preserving maximal residual foot length is an important goal when performing large debridement or minor amputation as it increases the patient's potential for rehabilitation and mobility (3).
Recently, we began using dermal substitutes to treat diabetic wounds with exposed healthy tendon and bone tissues following surgical debridement as treatment for acute infection. This retrospective study serves to evaluate the utility of a specific dermal substitute for preserving maximal foot length.
PATIENTS AND METHODS
Protocol
All patients referred to our Diabetic Foot Center for rest pain and/or foot ulcer or gangrene were assessed for sensory–motor neuropathy, infection and chronic critical limb ischaemia (CLI). Sensory–motor neuropathy and chronic CLI diagnosis were defined previously (1).
Infection diagnosis and treatment: first surgical step
The presence of local cellulitis, erythema, foul odour, warmth and/or purulence was used to indicate infection (4). If a deep space abscess was suspected upon initial examination, a small incision and probe exploration were performed. The presence of acute infection, such as abscess, wet gangrene or necrotising fasciitis based on the Infectious Disease Society of America (IDSA) classification of moderate and severe infection (4) indicated immediate surgical debridement in an operating room, which took place within 6–8 hours of admission. After draining any purulence, the lateral, central, medial and plantar compartments were explored. In the operating theatre, the surgeon, on the basis of the vital health of soft and bone tissue, decided whether to perform a minor amputation to achieve a primary closure (i.e. a Lisfranc amputation) or to try to save maximal foot length with a more distal amputation (i.e. transmetatarsal (TM) amputation), even if bone and tendon exposure was present that could be covered by a dermal regeneration template (DRT). Picture 2 shows a typical case of distal TM amputation with bone exposure instead of proximal TM or Lisfranc amputation with immediate surgical wound closure. The degree of amputation, if deemed necessary, was based on the amount of apparently non infected vital tissue. Wound closure was not attempted at this point because of the risk of infection.
A biopsy sample was obtained for culture prior to use of antiseptic. Broad spectrum antibiotic therapy consisting of piperacillin– tazobactam and fluoroquinolone was administered immediately following incision and drainage (5) and adjusted according to the cultures. Osteomyelitis was ruled out through plain X‐rays obtained on admission and 4 weeks after discharge.
Application of dermal substitute: second surgical step
According to the method above, when vital tendon and bone tissue remained exposed and when it was considered possible to carry out a more distal amputation instead of primary closure with a more proximal amputation, the lesion was covered with a dermal substitute (Integra® Dermal Regeneration Template, Integra LifeSciences Corporation, Plainsboro, NJ), provided that local and systemic infections were under control as indicated by subsidence of fever, normalisation of leukocyte count and disappearance of clinical signs of inflammation in the foot.
The Integra® Dermal Regeneration Template consists of a layer of bovine type I collagen chemically modified with glycosaminoglycans and covered with an adherent layer of silicone. The collagen matrix serves as a DRT and the silicone functions as an artificial epidermal barrier to fluid. In cases of plantar closure or wound, the patient was discharged with a non removable fiberglass non weight‐bearing cast. In cases of dorsal or lateral suture, the patient was discharged after receiving a post‐surgical shoe (6). After the neodermis was formed, the silicone layer was removed and patients underwent skin grafting an average of 21 days after DRT grafting.
Revascularisation procedure
All patients with CLI, in accordance with Inter‐Society Consensus for the Management of Peripheral Arterial Disease (TASC II) criteria (7), were referred for angiographic study. If an obstruction greater than 50% of vessel diameter was present, peripheral transluminal angioplasty (PTA) was performed as first choice revascularisation procedure during the same session, if possible. When PTA was not feasible, a bypass graft (BPG) was considered. The revascularisation outcome was measured by means of TcPO2 (Transcutaneous oxygen pressure) value after the procedure other than by means of the clinical and angiographic result.
Wound healing
Complete wound healing was defined as complete re‐epithelialisation.
Limb salvage
Limb salvage was considered successful if plantar standing was maintained (bipodalic stance), even when salvage was achieved by a below‐the‐ankle amputation 8, 9. Above‐the‐ankle amputation was considered a major amputation.
Patients whose wounds were not associated with bone and tendon exposure were excluded as these types of wounds often heal with conservative treatment (adequate dressings or skin graft). Because the outcome measured in this study was preservation of maximal residual stump length, patients with heel lesions were excluded.
Informed consent
Each patient provided informed written consent for every surgical procedure.
Follow‐up
All wounds were examined 5, 10 and 15 days after application of the dermal substitute. After recovery, patients wore specially designed, extra‐depth rocker shoes with customised insoles made of Alkafoam, a material derived from plastazote that can absorb high‐pressure points. The shoe leather is thermoformable, allowing it to adjust to toe and foot deformities (10).
Variables
Data on type, duration and pharmacological treatment of diabetes, presence of neuropathy, CLI, renal insufficiency, and history of cardiac disease and arterial hypertension were recorded. Laboratory variables evaluated were blood glucose level on admission, serum glycosylated haemoglobin, creatinine, C‐reactive protein and leukocyte count.
Statistical methods
For continuous variables, means and SDs were calculated; for discrete variables, the frequencies were calculated. The difference between the potential amputation level required for immediate surgical wound closure by first intention (without the dermal substitute) and the amputation level performed in patients who underwent the DRT grafting was evaluated by the Pearson's chi‐square test for trends. Stata 7.0 software (StataCorp LP, College Station, TX) was used for statistical calculations and analyses.
RESULTS
From 1 January to 31 December 2008, 393 patients admitted to our Diabetic Foot Center underwent surgical treatment for diabetic foot syndrome; 125 of these presented with an acute foot infection requiring immediate surgical debridement. Thirty (24%) of these 125 patients underwent immediate surgical debridement in the operating room that resulted in exposed tendon and/or bone tissues. In such cases, surgical wound closure would usually require a minor amputation or a more proximal amputation than that performed during urgent debridement (1, 2, 3). Table 1 reports patient characteristics and the University of Texas Diabetic Foot Classification of the foot lesions. Culture results identified polymicrobic infection in 15 of 30 patients (50%; Table 2).
Figure 1.
Severe diabetic foot infection (first sequence); urgent surgical debridement with residual bone and tendon exposure (second sequence); graft with Integra (third sequence); wound healing (fourth sequence). Potentially, a minor amputation (plus a skin graft) would have allowed an immediate surgical closure.
Figure 2.
(A) Diabetic foot infection (fore and midfoot); (B) urgent surgical debridement with metatarsals exposure after a distal transmetatarsal amputation; (C) graft with Integra; (D) results after the silicon layer removal: bones are covered by a neodermis; (E) wound healing; (F) at follow‐up. Even in this case, a more proximal amputation—proximal transmetatarsal amputation—would have allowed an immediate surgical closure.
Figure 3.
(A) Urgent surgical debridement because of the diabetic foot infection in the plantar and medial aspect of the foot; (B) graft with Integra; (C) after skin graft.
Table 1.
Demographic and clinical characteristics of followed patients (N = 30) with acute foot infection on admission
| Variables | Patients (N = 30) |
|---|---|
| Age (years) | 65·10 ± 13·34 |
| Females (n) | 8 (26·0%) |
| Insulin therapy (n) | 22 (73·3%) |
| Diabetes duration (years) | 16·4 ± 11·9 |
| Glycemia (mg/dl) | 203·1 ± 87·9 |
| Glycosylated haemoglobin (%HbA1c) | 8·3 ± 1·6 |
| Sensory–motor neuropathy (n) | 30 (100%) |
| Critical limb ischaemia (n) | 16 (53·3%) |
| Creatinine (mg/dl) | 1·18 ± 0·44 |
| Dialysis (n) | 0 (0%) |
| Antihypertensive therapy (n) | 11 (36·6%) |
| Cardiac disease (n) | 14 (46·6%) |
| Polymerase chain reaction | 9·6 ± 8·6 |
| White count cells (×10−3/mm) | 11·6 ± 5·7 |
| TUC Grade III Stage B (n) | 14 |
| TUC Grade III Stage D (n) | 16 |
TUC, Texas University Classification.
Data are mean ± 1 SD or % TUC.
Table 2.
Bacterial culture results, n (%)
| Staphylococcus aureus | 18 (60) |
| Candida albicans | 5 (16·6) |
| Streptococcus anginosus | 2 (6·6) |
| Streptococcus agalactiae | 2 (6·6) |
| Enterococcus faecalis | 4 (13·3) |
| Escherichia coli | 1 (3·3) |
| Corynebacterium spp. | 4 (13·3) |
| Staphylococcus epidermidis | 2 (6·6) |
| Dermacoccus | 1 (3·3) |
| Alcaligenes faecalis | 1 (3·3) |
| Citrobacter koseri | 1 (3·3) |
| Wautersia paucula | 1 (3·3) |
| Bacillus spp. | 1 (3·3) |
| Staphylococcus hominis | 1 (3·3) |
| Klebsiella oxytoca | 1 (3·3) |
Revascularisation was performed for the 16 patients (53·3%) who presented with CLI (TcPO2 values: admission = 13·6 ± 7·5 mmHg; post‐revascularisation = 47·06 ± 9·4 mmHg; P≤ 0·0001). Twelve patients underwent PTA and four underwent BPG. Revascularisation procedures were performed within 2 days of surgical debridement.
After an average of 4·4 ± 2·1 days following surgical debridement, all 30 patients underwent the dermal substitute grafting to cover exposed tendon and bone tissues. Secondary dressings were changed on post‐grafting days 5, 10 and 15 using the DRT. After the wound had filled with a sufficient quantity of granulation tissue (an average of 21 days post‐dermal substitute grafting), and if no complications had occurred, the silicone layer was removed and a skin graft was performed.
Wound healing
Complete wound healing occurred in 26 of the 30 patients (86·7%). The average healing time was 74·1 ± 28·9 days (range 35–136 days) following urgent surgical debridement.
Table 3 summarises the amputation levels potentially required for immediate wound closure and those required after application of the DRT. Four individuals (two with neuropathy and two with ischaemia) who had previously undergone amputation and dermal substitute grafting required a more proximal amputation. A Chopart amputation was performed to treat local infection in one patient with previous TM amputation; a TM amputation was performed in two patients who had previously undergone first ray amputation and one patient with previous TM amputation underwent a Chopart amputation because of the unsuccessful coverage of the exposed bone.
Table 3.
Surgical procedures and amputation level in the study population (N = 30) potentially required for immediate primary wound closure and obtained with the dermal substitute
| Amputation levels potentially required for immediate wound closure | Amputation level or debridement in patients treated with the dermal substitute | |
|---|---|---|
| 1° ray | Debridement without amputation | χ 2 = 18·0;P = 0·003 |
| Proximal transmetatarsal | Distal transmetatarsal | |
| 5° ray | Debridement without amputation | |
| Chopart | Debridement without amputation | |
| Distal transmetatarsal | 5° ray | |
| Distal transmetatarsal | Debridement without amputation | |
| Distal transmetatarsal | Debridement without amputation | |
| Distal transmetatarsal | 1° ray | |
| Distal transmetatarsal | 1° ray | |
| Chopart | Lisfranc | |
| Distal transmetatarsal | 5° ray | |
| Lisfranc | Distal transmetatarsal | |
| Chopart | Lisfranc | |
| Distal transmetatarsal | 5° ray | |
| Distal transmetatarsal | 5° IV ray | |
| Chopart | Proximal transmetatarsal | |
| Distal transmetatarsal | 5° ray | |
| Proximal transmetatarsal | Distal transmetatarsal | |
| Proximal transmetatarsal | Distal transmetatarsal | |
| 5° ray | Debridement without amputation | |
| Proximal transmetatarsal | Distal transmetatarsal | |
| Proximal transmetatarsal | Distal transmetatarsal | |
| Lisfranc | Distal transmetatarsal | |
| 4° ray | Debridement without amputation | |
| Proximal transmetatarsal | Distal transmetatarsal | |
| 5° ray | Debridement without amputation | |
| Distal transmetatarsal | 4° ray | |
| Proximal transmetatarsal | Distal transmetatarsal | |
| Lisfranc | Distal transmetatarsal | |
| 2° ray | Debridement without amputation |
Limb salvage
No patient underwent major amputation.
DISCUSSION
Despite improvements in the management of the diabetic foot, the presence of ischaemia or infection, which increase the risk of amputation and mortality, remains a challenge for clinicians 11, 12. In our experience, these complications most often result from delayed treatment. Treatment delay allows the rapid spread of infection and tissue necrosis, resulting in severe loss of substance (13). In these cases, limb salvage requires aggressive debridement with or without minor amputation, frequently at very proximal levels. In such situations, the aim is to preserve maximal residual stump length, thereby providing patients with the greatest possibility of rehabilitation and continued mobility. While providing good results in the non diabetic population, plastic surgery techniques such as regional flaps and free flaps are not always applicable for diabetic patients as these patients often present with accompanying complications (such as poor vascularisation of the foot) and/or comorbidities, most of which are cardiovascular (14). Thus, these techniques are suitable only for well‐selected diabetic patients (15).
The use of dermal substitutes in the treatment of patients with burns or oncological surgical defects has been previously studied 16, 17. Dermal substitutes have also been evaluated for the treatment of diabetic patients with neuropathic plantar ulcer (18). The present study is the first to evaluate the efficacy of dermal substitutes for preserving maximal foot length in diabetic patients presenting with exposed tendon and bone tissues. Relative to techniques that use regional flaps and free flaps, dermal substitutes offer unique advantages in terms of ease of use and decreased invasiveness.
In this study, complete healing occurred in almost 87% of patients treated with the DRT; at present, all these patients remain ambulatory with shoes prescribed as secondary prevention. In the remaining four patients, all of whom had undergone previous amputation, the presence of infection or unsuccessful coverage of exposed tendon and bone tissues necessitated a proximalisation procedure. However, no major amputation was performed, which constitutes a very positive result considering the prognoses for patients with University of Texas Classification Grade 3, Stage B and D wounds (11).
The results for healing time are quite encouraging. In patients presenting with large loss of substance because of gangrene, infection and/or ischaemia, the time required to achieve healing is usually very long 19, 20. In the present study, the average healing time was a little over 2 months. The patients were followed regularly, and none experienced ulcer recurrence or complications such as osteomyelitis of the covered wound.
At present, the follow‐up period is relatively short. Continued evaluation of all patients will allow us to draw definitive conclusions. One might hypothesise that similar results could have been achieved using advanced dressings or bioengineered skin substitutes. However, the question remains as to whether such dressings can cover the tendon and bone tissues adequately and the effect of these types of dressing on healing time 21, 22, 23. The results presented here indicate that the use of dermal substitutes could be an effective part of a comprehensive programme for management of diabetic foot ulcers; a programme that would also include optimal metabolic control, proper prevention and/or prompt and aggressive treatment of infection, prompt revascularisation to improve foot blood flow in cases of CLI and proper offloading of foot lesions.
In conclusion, the use of the dermal substitute Integra® in the management of exposed tendon and bone tissues following treatment for deep wound infections in diabetic patients allowed timely wound healing and preserved maximal foot length, improving walking ability in the majority of the patients. Continued follow‐up of these patients will allow assessment of long‐term relapse and complication rates. Such treatment could constitute part of the comprehensive management of diabetic wounds.
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