Efficacy of Hyperbaric Oxygen Therapy in Diabetic Foot Ulcers Based on Wagner Classification

Diabetic foot ulcer is a common chronic complication of diabetes mellitus. In addition to conventional primary therapy, there are adjuvant therapy methods such as hyperbaric oxygen therapy for the healing of diabetic foot ulcer wounds. The present study aimed to determine the efficacy of hyperbaric oxygen therapy in diabetic foot ulcers based on Wagner classification. It was performed retrospectively from prospectively collected data. One hundred thirty patients with diabetic foot ulcers were assessed in 2 groups: 1 group received hyperbaric oxygen therapy; the other group did not. Patients were examined according to age, sex, ulcer grade based on Wagner classification; ulcer healing status; whether hyperbaric oxygen therapy was received; duration of diabetes in years; HbA1C, sedimentation, C-reactive protein levels; and presence of accompanying diseases, including peripheral arterial disease, chronic obstructive pulmonary disease, hypertension, chronic kidney disease, neuropathy, and retinopathy. The mean follow-up period was 19.5?±?4.45 months (range 12 to 28 months). Seventy-one (54.6%) patients received hyperbaric oxygen therapy, and 59 (45.4%) patients did not. All patients in Wagner grade 2 healed in both groups. In the group that received hyperbaric oxygen therapy for grade 3 and 4 patients, 35 (87.5%) and 11 (84.6%) healed, respectively. In total, 60 (84.5%) patients in the group that received hyperbaric oxygen therapy healed. The subgroup comparison conducted according to Wagner classification revealed no differences between the 2 groups of grades 2 and 5 patients. It also revealed that treatment had higher levels of efficacy in the healing of ulcers in grade 3 and 4 patients.     

Treatment of diabetic foot complications with hyperbaric oxygen therapy: A retrospective experience

BackgroundThe aim of this study is to evaluate the role of hyperbaric oxygen in the treatment of diabetic foot ulcers.MethodsWe performed a retrospective observational study of all patients with diabetic foot ulcers treated at the Institution's hyperbaric chamber between January 2010 and August 2012. Patient data was obtained upon patient hospital visit and prospective clinical record consultation.ResultsTwenty-six foot lesions including 13 foot ulcers Wagner grade 2 or greater and 13 amputation stump ulcers were submitted to hyperbaric oxygen therapy between January 2010 and August 2012 in our Institution. Of these, 23 foot lesions completed treatment and complete epithelialization of the primary lesion was achieved in 15 (65%). The mean healing period since the first hyperbaric oxygen therapy session was 16 weeks. Above-ankle amputations were performed in 3 limbs and transmetatarsal amputations in 2 limbs.ConclusionHyperbaric oxygen may be associated with ulcer healing in selected diabetic foot ulcers with impaired cicatrization.     

Low-level laser therapy as an adjunct to conventional therapy in the treatment of diabetic foot ulcers

Foot ulcers are serious complications of diabetes mellitus (DM) and are known to be resistant to conventional treatment. This study was conducted to evaluate the efficacy of low-level laser therapy (LLLT) for the treatment of diabetic foot ulcers in a tertiary care centre (Department of Surgery, Mahatma Gandhi Memorial Medical College and Maharaja Yashwantrao Hospital, A.B. Road, Indore). A total of 30 patients with type 2 DM having Meggitt-Wagner grade I foot ulcers of more than 6 weeks duration with negative culture were studied. Patients were randomized into two groups of 15 each. Patients in study group received LLLT (660?±?20 nm, 3 J/cm²) along with conventional therapy and those in control group were treated with conventional therapy alone. The primary outcome measure was the absolute and relative wound size reduction at 2 weeks compared to the baseline parameter. Percentage ulcer area reduction was 37?±?9% in the LLLT group and 15?±?5.4% in the control group (p?<?0.001). For ～75% of wounds of the treatment group, wound area reduction of 30–50% was observed. In contrast, for the control group, ～80% of wounds showed a wound area reduction of <20% on day 15. Further, the wounds with initial wound area 1000–2000 mm² seems to have better final outcome than the groups with larger areas. The treated groups showed higher amount of granulation than the control group. The results suggest that LLLT is beneficial as an adjunct to conventional therapy in the treatment of diabetic foot ulcers.     

A retrospective study of diabetic foot ulcers treated with hyperbaric oxygen therapy

A retrospective review of patient medical records was conducted to assess what factors influence the outcomes of diabetic foot ulcers treated with hyperbaric oxygen (HBO) therapy. Patients referred to the Diving Diseases Research Centre for HBO therapy for the treatment of diabetic foot ulcers during a 2‐year period were included in this study. Data collected from 30 sets of patient records were entered into SPSS and statistical analysis was undertaken to investigate whether any underlying pathologies or confounding factors appeared to influence patient outcome. A 73·3% of patients achieved a successful outcome of partial healing, major amputation no longer required, amputation level lower than anticipated prior to HBO or healing at the end of HBO therapy and 70% remained successful 3 months later. A 13·3% of patients were lost to follow‐up at 3 months and one patient (3·3%) had a major amputation. Steroid therapy, peripheral vascular disease, previous minor amputation, type of diabetes, previous HBO therapy, larvae therapy, the use of interactive dressings and haemoglobin A1c levels were all observed to have had a significant relationship with patient outcome (P < 0·05). These results were compared with data from other published research conducted in this area on similar patient groups. A larger scale study focussing on the factors found to be significant in this study is recommended. An improvement of patient documentation would allow patient outcomes to be more consistently monitored in the future.     

Anterior superior iliac spine distraction for severe and recalcitrant diabetic foot ulcers

PurposeThe study aimed to introduce anterior superior iliac spine distraction to treat severe and recalcitrant diabetic foot ulcers. For comparison, we also included another group of diabetic foot ulcers treated with proximal tibial cortex transverse distraction.MethodsFrom February 1998 to February 2020, 87 patients (87 feet) with severe and recalcitrant diabetic foot ulcers were treated. The mean age of patients at surgery was 64 years (range, 47 to 87 years). The severity of the narrowed artery was assessed using the ankle-brachial index test. For comparison, another group of 91 patients (91 diabetic foot ulcers) treated with proximal tibial cortex transverse distraction was included.ResultsThe mean preoperative ankle-brachial indexes of the two groups were 0.41±0.07 and 0.39±0.05 (OR 0.65 [95% CI -0.77 to 1.58]; P=0.62), respectively. The mean preoperative limb pain was 3.42±2.84 cm and 3.52±3.11 cm (OR 1.54 [95% CI -077 to 1.35]; P=0.083), respectively. At the 2-year follow-up visit, ulcers healed in 72 (83%) and 74 (81%) patients, respectively (P=0.188). The mean postoperative limb pain was 0.52±0.23 cm and 0.49±0.41 cm (OR 2.32 [95% CI -0.27 to 1.66]; P=0.078), respectively. Pin-site infection occurred in 2 patients and 8 patients (P=0.09), respectively. Ulcer recurrence occurred in 13 (15%) patients and 15 (16%) patients (P=0.205), respectively.ConclusionsAnterior superior iliac spine transverse distraction may be an effective alternative treatment for severe and recalcitrant diabetic foot ulcers. It may be associated with fewer distraction-site complications than proximal tibial cortex transverse distraction.Level of evidenceTherapeutic study, Level IIa.     

Prevention and treatment of diabetic foot wounds

The diabetic foot ulcer is one of the most common and devastating complications of diabetes mellitus. These ulcers account for most of the hospital admissions for patients with diabetes, and they represent a common precursor for amputation. When a diabetic foot ulcer becomes infected, gangrene and amputation can follow in rapid succession. Recent reviews concerning diabetic foot lesions and amputations have stressed the magnitude and importance of aggressive management. This management is complicated, and typically requires radical débridement, appropriate antibiotics, non-weight-bearing, and vascular surgery when indicated. A variety of adjunctive therapy can be helpful, including hyperbaric oxygen and topical growth factors. The most important step in preventing ulceration of the foot is patient education in foot care.     

Successful treatment of diabetic foot ulcers with low-level laser therapy

IntroductionDiabetic foot ulcers, being notoriously difficult to cure, are one of the most common health problems in diabetic patients.There are several surgical and medical options already introduced for treatment of diabetic foot ulcers.Low-level laser therapy (LLLT) has been suggested as a promising treatment option for open wounds. However, there is very little work on the efficacy of low-level laser therapy for this type of open wounds.We report herein seven cases of grades II and III diabetic foot ulcer completely treated with LLLT.Materials and methodsSeven Type 2 diabetic patients (four males: mean age, 63 years; three females: mean age, 61.14 years) with grades II and III diabetic foot ulcers were treated with low-level laser therapy. The mean duration of diabetes was 10.5 years and the ulcers were present from average 6.5 months ago. The mean value for glycosylated hemoglobin (HbA1C) also was 8.14 mg/dl (range: 6–12.2) and foot blood flow in Doppler ultra-sonography were normal.We used low-level laser therapy through local irradiation of the ulcer bed with red light (660 nm; power: 25 MW; 0.6–1 J/cm²) and ulcer margins with infrared laser (980 nm; power: 200 MW; 4–6 J/cm²), along with intravenous laser irradiation with red light laser (650 nm; power: 1.5 MW) for 15–20 min, in addition to laser acupuncture with infrared laser (1 J/cm²) for LI-11, LI-6, SP-6, PC-6, ST-36 and GB-34 points.Sessions were every other day for 10–15 sessions (Route 1) and then continuing the course twice weekly (Route 2) until complete recovery was achieved.ResultsAfter approximately 19 sessions (mean Route 1 sessions ≈15; mean Route 2 sessions ≈10), complete recovery was achieved in all cases and there was no relapse or other problem with ulcers after approximately 6 months (range: 2–10 months) of follow-up. With this treatment regimen, there were no side-effects reported by the patients.ConclusionLow-level laser therapy could be a safe and effective method for treatment of diabetic foot ulcers. Clinical trials with higher sample size are proposed to more evaluate the efficacy of low-level laser therapy in treatment of this type of wounds.     

Hyperbaric oxygen therapy of diabetic foot ulcers, transcutaneous oxymetry in clinical decision making

The foot ulcer is one of most common and devastating complications of diabetes and is associated with considerable morbidity and mortality. The major causes of these ulcers are ischemia/hypoxia, neuropathy, and infection, and they often coexist. Despite conventional therapy including revascularization procedures when appropriate, three situations lead frequently to amputation: persistent critical limb ischemia, soft tissue infection, and impaired wound healing from osteomyelitis. In these conditions, hyperbaric oxygen therapy may be used as an adjunctive treatment and is associated with a better outcome. Randomized, prospective, controlled trails have shown the benefit of hyperbaric oxygen therapy in diabetic ulcers of the lower extremity. Transcutaneous oxygen measurement performed under hyperbaric oxygen therapy has a prognostic significance when used to select patients who are the most likely to benefit from therapy. Hyperbaric oxygen should be added to conventional treatment if the transcutaneous oxygen tension close to the trophic lesion in 2.5 ATA hyperbaric oxygen is over 200 mmHg. Peri-wound transcutaneous oxygen tensions over 400 mmHg in 2.5 ATA hyperbaric oxygen or over 50 mmHg in normobaric pure oxygen predict healing success with adjuncted hyperbaric oxygen therapy with high accuracy.     

Treatment of diabetic foot ulcers with hyperbaric oxygen

The delivery of oxygen to the wound site is crucial in healing diabetic foot ulcers, and impairment of this process in people with diabetes leads to delayed wound repair. Hyperbaric oxygen therapy works by elevating the plasma oxygen level. Fibroblasts synthesise and modify collagen, and both these activities require relatively high partial pressures of oxygen. Hyperbaric oxygen can promote healing by stimulating fibroblast activity and collagen formation. Increasing oxygen tensions also has a direct and toxic effect on anaerobes, therefore hyperbaric oxygen therapy has a special role in treating diabetic foot infections. Studies on hyperbaric oxygen therapy in general show it to be a beneficial adjunctive therapy for diabetic foot ulcers. However much of the work is anecdotal and more controlled trials are required.     

Maggot debridement therapy with Lucilia cuprina: a comparison with conventional debridement in diabetic foot ulcers

This is prospective case–control study of more than 18 months performed to assess the effectiveness of maggot debridement therapy (MDT) with the sterile larvae of Lucilia cuprina (a tropical blowfly maggot) for the treatment of diabetic foot ulcers. Literature thus far has only reported results with the temperate maggot, Lucilia sericata. This study documents outcome in diabetic foot wounds treated with maggot debridement versus those treated by conventional debridement alone. In this series of 29 patients treated with MDT, 14 wounds were healed, 11 were unhealed and 4 were classified under others. The control group treated by conventional debridement had 30 patients of which 18 wounds were healed, 11 unhealed and 1 classified under others. There was no significant difference in outcome between the two groups. The conclusion that can be made from this study is that MDT with L. cuprina is as effective as conventional debridement in the treatment of diabetic foot ulcers. It would be a feasible alternative to those at high risk for surgery or for those who refuse surgery.     

Angiosome‐targeted revascularisation in diabetic foot ulcers

Peripheral vascular disease is a common complication of type 2 diabetes and is often more severe and diffuse than in non‐diabetic individuals with a higher risk of major amputations in the lower limbs. Diabetic foot revascularisation using both traditional bypass surgery and endovascular therapy are often burdened by the failure and the inevitable subsequent massive amputation. In this study, we examined the clinical response of diabetic patients with critical limb ischaemia and extended ischaemic wounds, treated with a new angiosome‐based revascularisation technique. In a 3‐year period, nine diabetic patients with imminent amputation threatening and foot ulcers with no feasible arterial revascularisation options were treated by the angiosome‐based surgical technique by means of deep vein arterialisation. The postoperative tcPO2 evaluation showed a mean increase in the cutaneous oxygen tension in all patients treated. The overall survival rates were 88·88%, 88·88% and 77·77% at 12, 24 and 36 months, respectively. Limb salvage was 100% at 1 year and steady at 88·88% thereafter. Surgical deep venous arterialisation might be considered as an extreme alternative to attempt tissue preservation in limbs unfit for conventional arterial revascularisations. This technique would give advantages to the patients in terms of better compliance to the minor amputations and thus avoiding major limb amputations.     

Manuka honey‐impregnated dressings in the treatment of neuropathic diabetic foot ulcers

In this study, we investigate the effect of manuka honey‐impregnated dressings (MHID) on the healing of neuropathic diabetic foot ulcers (NDFU). A total of 63 Caucasians, type 2 diabetic patients followed up in the diabetic foot outpatient clinic comprised the study population. Patients were randomised in two groups as follows: group I patients were treated with MHID and group II patients were treated with conventional dressings (CD). The patients were followed up on a weekly basis for 16 weeks. Mean healing time was 31 ± 4 days in group I versus 43 ± 3 days in group II (P < 0·05). In group I patients 78·13% of ulcers became sterile during the first week versus 35·5% in group II patients; the corresponding percentages for weeks 2, 4 and 6 were 15·62% versus 38·7%, 6·25% versus 12·9% and 0% versus 12·9% respectively. The percent of ulcers healed did not differ significantly between groups (97% for MHID and 90% for CD). MHID represent an effective treatment for NDFU leading to a significant reduction in the time of healing and rapid disinfection of ulcers.     

The Long-Term Outcomes Following the Application of Intralesional Epidermal Growth Factor in Patients With Diabetic Foot Ulcers

Epidermal growth factor is used as an adjuvant to close the wound in addition to standard care in diabetic foot ulcers. This study aimed to investigate the long-term outcomes after intralesional epidermal growth factor injections in the treatment of diabetic foot ulcers. Thirty-six feet of 34 patients (n?=?34) with diabetic foot ulcers were included. Patient demographics, Wagner classifications, recurrence and amputation rates, Foot Function Index, Short Form 36, and American Academy of Orthopedic Surgeons Foot and Ankle Module scores were evaluated at the final follow-up examination. The mean age was 61.000 ± 13.743 years. The mean duration of wounds was 240.200 ± 146.385 days. A mean of 18.125 ± 4.494 (range 9 to 24) doses were applied. Wound closure was achieved in 33 of the 36 (91.7%) lesions. A complete response (granulation tissue >75% or wound closure) was observed in 29 (87.9%) lesions. The mean time to wound closure was 52.08 ± 10.65 (range 25 to 72) days. At the 5-year follow-up, 4 patients were lost to follow-up because of exitus owing to diabetic complications. Of the remaining 29 patients, 27 were ulcer free. In 2 patients (2 lesions, 6.9%) toe amputation was performed due to ischemic necrosis. The mean Foot Function Index, American Academy of Orthopedic Surgeons Foot and Ankle Core Scale, and AAOS Shoe Comfort Scale scores were 55.40 ± 12.15, 65.92 ± 17.56, and 56.42 ± 11.98, respectively. Complete wound healing and a low recurrence and amputation rates could be obtained with intralesional epidermal growth factor added to the standard treatment protocol.     

A prospective study: hyperbaric oxygen therapy in diabetics with chronic foot ulcers

Research suggests that hyperbaric oxygen therapy may have beneficial effects on ulcer healing and amputation rates in diabetic patients. This paper describes the design of a study that is evaluating its effects on chronic diabetic foot ulcers.     

Can major amputation rates be decreased in diabetic foot ulcers with hyperbaric oxygen therapy?

Although hyperbaric oxygen therapy has been used for diabetic foot ulcer since the 1980s, there is little information on its efficacy. The aim of this study is to evaluate whether hyperbaric oxygen can decrease major amputation rates and to determine the predictive factors. A total of 184 consecutive patients were treated with hyperbaric oxygen therapy as an adjunct to standard treatment modalities for their diabetic foot ulcer. Of these patients, 115 were completely healed, 31 showed no improvement and 38 underwent amputation. Of the amputations, nine (4.9%) were major amputations (below knee) and 29 were minor. Major amputations were associated with the Wagner grade (p < 0.0001), with the age of the patients (p = 0.028) and with the age of the wounds (p = 0.018). Hyperbaric oxygen therapy can help to reduce the major amputation rates in diabetic foot ulcer. However, further large, multicentre, randomised controlled studies are needed to make more accurate conclusions.     

Hyperbaric oxygen therapy for nonischemic diabetic ulcers: A systematic review

Diabetic foot ulcers are a common complication of diabetes, which affects 25% of patients and may ultimately lead to amputation of affected limbs. Research suggests hyperbaric oxygen therapy improves healing of these ulcers. However, this has not been reflected in previous reviews, possibly because they did not differentiate between patients with and without peripheral arterial occlusive disease. Therefore, we performed a systematic review of published literature in the MEDLINE, Embase, and Cochrane CENTRAL databases on nonischemic diabetic foot ulcers with outcome measures including complete ulcer healing, amputation rate (major and minor), and mortality. Seven studies were included, of which two were randomized clinical trials. Two studies found no difference in major amputation rate, whereas one large retrospective study found 2% more major amputations in the hyperbaric oxygen group. However, this study did not correct for baseline differences. Two studies showed no significant difference in minor amputation rate. Five studies reporting on complete wound healing showed no significant differences. In conclusion, the current evidence suggests that hyperbaric oxygen therapy does not accelerate wound healing and does not prevent major or minor amputations in patients with a diabetic foot ulcer without peripheral arterial occlusive disease. Based on the available evidence, routine clinical use of this therapy cannot be recommended. However, the available research for this specific subgroup of patients is scarce, and physicians should counsel patients on expected risks and benefits. Additional research, focusing especially on patient selection criteria, is needed to better identify patients that might profit from this therapy modality.     

Intralesional allogeneic adipose-derived stem cells application in chronic diabetic foot ulcer: Phase I/2 safety study

BackgroundImpaired wound healing is a major cause of morbidity in diabetic patients by causing chronic ulcers. This study aimed to investigate the safety and outcomes after intralesional allogeneic adipose-derived mesenchymal stem cells injection in chronic diabetic foot ulcers.MethodsTwenty patients (12 male and eight female) were involved in the study. We randomized the patients into two groups of 10 patients each. The study group was treated with allogeneic adipose-derived mesenchymal stem cells injection with standard diabetic wound care. The control group received only standard diabetic wound care. Patient demographics, wound characteristics, wound closure time, amputation rates and clinical scores were evaluated.ResultsThe mean age was 57.3 ± 6.6 years. The mean follow-up duration was 48.0 (range, 26–50) months. Wound closure was achieved in 17 of 20 lesions (study group, 9 lesions; control group, 8 lesions; respectively). The mean time to wound closure was 31.0 ± 10.7 (range, 22–55) days in the study group, 54.8 + 15.0 (range, 30–78) days in the control group (p = 0.002). In three patients, minor amputations were performed (one patient in study group; two patients in the control group, p = 0.531). There was a significant difference between groups in terms of postoperative Short Form 36- physical functioning (p = 0.017) and Short Form 36-general health (p = 0.010).ConclusionAllogeneic adipose-derived mesenchymal stem cells injection was found to be a safe and effective method with a positive contribution to wound-healing time in the treatment of chronic diabetic foot ulcers.     

Perceptions of hyperbaric oxygen therapy among podiatrists practicing in high‐risk foot clinics

Foot ulceration is a devastating and costly consequence of diabetes. Hyperbaric oxygen therapy is recognised as an adjunctive therapy to treat diabetes‐related foot ulceration, yet uptake is low. Semi‐structured interviews were conducted with 16 podiatrists who manage patients with foot ulcers related to diabetes to explore their perceptions of, and the barriers/facilitators to, referral for hyperbaric oxygen. Podiatrists cited logistical issues such as location of facilities as well as poor communication pathways, lack of delegation and lack of follow up when patients presented for hyperbaric treatment. In general, podiatrists had an understanding of the premise of hyperbaric oxygen therapy and evidence to support its use but could only provide very limited citations of key papers and guidelines to support their position. Podiatrists stated that they felt a patient was lost from their care when referred for hyperbaric oxygen and that aftercare might not be adequate. Improved referral and delegation pathways for patients presenting for hyperbaric oxygen, as well as the provision of easily accessible evidence to support this therapy, could help to increase podiatrists’ confidence in deciding whether or not to recommend their patients for hyperbaric oxygen therapy.     

Dose-dependent hyperbaric oxygen stimulation of human fibroblast proliferation

Diabetic wounds are characterized by a prolonged wound healing process with insufficient formation of granulation tissue. Systemic hyperbaric oxygen therapy has been observed to improve the healing of these wounds. However, the mechanism(s) responsible for these findings are not yet fully elucidated. In the present study we have studied the in vitro effects of hyperbaric oxygen on proliferation of human fibroblasts from normal skin and from chronic foot ulcers in non-insulin-dependent diabetics. A 1-hour exposure to hyperbaric oxygen at oxygen pressures between 106 and 300 kPa (795 to 2250 mm Hg) increased the proliferation in both diabetic and normal fibroblasts. The stimulatory effect was dose-dependent, with a peak increase in cell proliferation at 250 kPa and 200 kPa for normal and diabetic cells, respectively. The effects were not due to hydrostatic pressure per se. These results suggest that hyperbaric oxygen could stimulate fibroblast activity in the diabetic wound, a finding that could explain the enhanced formation of granulation tissue seen clinically in wounds treated with hyperbaric oxygen. We also speculate that mechanisms other than just increased oxygen availability may be responsible for our findings.     

The Role of Hyperbaric Oxygen Therapy in Ischaemic Diabetic Lower Extremity Ulcers: a Double-blind Randomised-controlled Trial

OBJECTIVE: ischaemic lower-extremity ulcers in the diabetic population are a source of major concern because of the associated high risk of limb-threatening complications. The aim of this study was to evaluate the role of hyperbaric oxygen in the management of these ulcers. METHOD: eighteen diabetic patients with ischaemic, non-healing lower-extremity ulcers were recruited in a double-blind study. Patients were randomly assigned either to receive 100% oxygen (treatment group) or air (control group), at 2.4 atmospheres of absolute pressure for 90 min daily (total of 30 treatments). RESULTS: healing with complete epithelialisation was achieved in five out of eight ulcers in the treatment group compared to one out of eight ulcers in the control group. The median decrease of the wound areas in the treatment group was 100% and in the control group was 52% (p=0.027). Cost-effectiveness analysis has shown that despite the extra cost involved in using hyperbaric oxygen, there was a potential saving in the total cost of treatment for each patient during the study. CONCLUSION: hyperbaric oxygen enhanced the healing of ischaemic, non-healing diabetic leg ulcers and may be used as a valuable adjunct to conventional therapy when reconstructive surgery is not possible.