Systemic Hyperbaric Oxygen Therapy Research Articles

Resistant Chronic Venous Leg Ulcers: Effect of Adjuvant Systemic Hyperbaric Oxygen Therapy Versus Venous Intervention Alone.

The aim of this study was to assess the adjuvant efficacy of adding systemic hyperbaric oxygen therapy (HBOT) to definitive venous intervention for healing of resistant chronic venous leg ulcers (VLUs). From 97 chronic VLUs, 63 were subjected to a pre-study standard wound care. Thirty three ulcers failed to achieve 50% size reduction, after the 4-weeks standard care, and were allocated to be treated with: HBOT plus venous intervention (n = 17), or venous intervention alone (n = 16). Primary outcomes were the change in ulcer area, complete healing frequency and time, as well as ulcer recurrence. There was a history of recurrent ulcer (82.3% vs. 69%) in HBOT versus venous intervention groups, respectively. The comparison between both groups with regard to area change showed non-significant difference after 3 months of therapy, while there was a significant difference at 6 and 12 months. A significant positive correlation was found between the HBO sessions numbers (20-40) and the rate of ulcer size reduction. Ulcer complete closure after 3 months was observed in (41.7%) of HBOT group, versus (23%) in venous intervention group; (p = 0.33). After 12 months, complete closure was observed in (83.3%) of HBOT group, versus (53.8%) in venous intervention group; (p = 0.02). The mean time of complete closure was significantly shorter in HBOT group, (p = 0.001). HBOT may be effective as adjuvant to venous intervention in treatment of chronic resistant VLUs, it should be reserved for persistent ulcer. Randomized controlled trials with larger numbers is still needed to elucidate its exact role and specific indications.

Australian guideline on wound healing interventions to enhance healing of foot ulcers: part of the 2021 Australian evidence-based guidelines for diabetes-related foot disease

BackgroundDiabetes-related foot ulceration (DFU) has a substantial burden on both individuals and healthcare systems both globally and in Australia. There is a pressing need for updated guidelines on wound healing interventions to improve outcomes for people living with DFU. A national expert panel was convened to develop new Australian evidence-based guidelines on wound healing interventions for people with DFU by adapting suitable international guidelines to the Australian context.MethodsThe panel followed National Health and Medical Research Council (NHMRC) procedures to adapt suitable international guidelines by the International Working Group of the Diabetic Foot (IWGDF) to the Australian context. The panel systematically screened, assessed and judged all IWGDF wound healing recommendations using ADAPTE and GRADE frameworks for adapting guidelines to decide which recommendations should be adopted, adapted or excluded in the Australian context. Each recommendation had their wording, quality of evidence, and strength of recommendation re-evaluated, plus rationale, justifications and implementation considerations provided for the Australian context. This guideline underwent public consultation, further revision and approval by ten national peak bodies.ResultsThirteen IWGDF wound healing recommendations were evaluated in this process. After screening, nine recommendations were adopted and four were adapted after full assessment. Two recommendations had their strength of recommendations downgraded, one intervention was not currently approved for use in Australia, one intervention specified the need to obtain informed consent to be acceptable in Australia, and another was reworded to clarify best standard of care. Overall, five wound healing interventions have been recommended as having the evidence-based potential to improve wound healing in specific types of DFU when used in conjunction with other best standards of DFU care, including sucrose-octasulfate impregnated dressing, systemic hyperbaric oxygen therapy, negative pressure wound therapy, placental-derived products, and the autologous combined leucocyte, platelet and fibrin dressing. The six new guidelines and the full protocol can be found at: https://diabetesfeetaustralia.org/new-guidelines/ConclusionsThe IWGDF guideline for wound healing interventions has been adapted to suit the Australian context, and in particular for geographically remote and Aboriginal and Torres Strait Islander people. This new national wound healing guideline, endorsed by ten national peak bodies, also highlights important considerations for implementation, monitoring, and future research priorities in Australia.

A Portable Oxygen Concentrator for Wound Healing Applications

Wound healing is a complex biological process that involves an organized cell assembly leading to tissue regeneration and repair, a process that requires oxygen. As has been reported in many studies, hypoxia delays wound healing; oxygen modulates the inflammatory response of the tissues and it serves as an infection control agent by enhancing the ability of leukocytes to kill bacteria when supplied in adequate amounts. In addition, it promotes collagen synthesis and stimulates angiogenesis. Most importantly, continuous oxygen application leads to wound closure, as has been shown in a number of clinical studies where closure rates as high as 80% have been observed for non-healing recalcitrant wounds. EPIFLO® (Ogenix, Beachwood, OH). (Figure 1) is a commercially available device that can deliver Transdermal Continuous Oxygen therapy and represents an inexpensive alternative to systemic hyperbaric oxygen therapy without the side effects of vasoconstriction, toxicity, and tissue destruction associated with the latter. EPIFLO is a light-weight (~100 g) electrochemical oxygen concentrator with no moving parts and silent operation. It generates continuously 3 mL/hour oxygen (98+% purity) and delivers to the wound site through a cannula tubing. It employs leading-edge oxygen ‘fuel cell’ concentration technology to stimulate tissue regenerative processes driving closure of delayed-healing acute or chronic wounds. This product is US FDA approved for a broad range of indications as a Class II Medical Device; prescribed on order of a physician. It is also CE, ISO 13485:2003 and CMDCAS (Canadian Medical Devices Conformity Assessment Scheme) Health Canada Certified The heart of the device is a Membrane Electrode Assembly (MEA) consisting of a perfluorosulfonic acid cation exchange membrane, such as NafionR, interposed between two high area electrodes made of finely divided Pt based metal catalysts (Figure 2). Atmospheric air composed mostly of ~ 21 % oxygen, 78 % nitrogen is exposed to the device through the slots in the seam formed between the lid and the bottom part of the enclosure, where when activated using a small battery, it promotes the reduction of dioxygen at the cathode and the oxidation of water at the anode to produce oxygen delivered through a suitable tubing to the wound. Since the cation exchange membrane has overall very low gas permeability, gases cannot permeate through the membrane, thus ensuring a higher than 98% purity of the product oxygen. This presentation will describe the critical steps involved in the bench-to-shelf process, invention to product, as well as the highly promising results found from its use in recalcitrant patients.

Hemodynamic profiles of intubated and mechanically ventilated carbon monoxide-poisoned patients during systemic hyperbaric oxygen therapy

BackgroundCarbon monoxide (CO) poisoning can be a life threatening condition. Systemic hyperbaric oxygen (HBO) therapy is used to induce CO detoxification. However, little is known about the hemodynamic response to HBO in severely intoxicated patients.MethodsWe retrospectively analyzed the medical records of 6 CO-poisoned patients treated with propofol, rocuronium bromide, and HBO. The HBO protocol comprised 3 HBO treatments (HBOT1 to HBOT3) within 24 hours. During all HBO sessions heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse blood pressure (ΔBP) were measured every five minutes. Non-parametric tests were used to compare data between HBO sessions.ResultsHR increased significantly as the number of HBOT increased, from 68 beats per minute (bpm) during HBOT1 to 77 and 86 bpm during HBOT2 and HBOT3, respectively (p < 0.05). In addition, while no significant change was found for DBP, both SBP and ΔBP showed a transient and significant increase during HBOT2, compared to HBOT1, that did not return to basal values during HBOT3.ConclusionBased on previous studies that have established the respective effects of rocuronium bromide, propofol, HBO, and CO alone on HR, SBP, and ΔBP, it is concluded that the hemodynamic responses observed in the present study are likely to be due to CO. If such, given that neither HR nor SBP and ΔBP returned to basal values by the end of HBOT3, it is suggested that more than 3 HBOT sessions could be necessary to provide full hemodynamic recovery in CO-poisoned patients.

Symmetrical peripheral gangrene and the use of systemic hyperbaric oxygen therapy

Symmetrical peripheral gangrene (SPG) is a rare but devastating condition when two or more distal sites become gangrenous, as the result of severe illness and treatment in critical care. The striking factor in SPG is that there is no occlusion of the major blood vessels to the affected limbs; the pathogenesis of the condition is not well understood and there are high reported mortality and amputation rates. Here we report the chronological progress report of a case of SPG, which affected both forefeet. This case report supports the view that early amputation should be avoided allowing for stabilisation of the gangrene so that no viable tissue is sacrificed. Further research is necessary to establish the pathogenesis and suitable treatment pathways.

PMD8 Efficacy of Systemic Hyperbaric Oxygen Therapy for Non-Healing Diabetic Ulcers of the Lower Limb: Systematic Review and Meta-Analysis

PMD8 Efficacy of Systemic Hyperbaric Oxygen Therapy for Non-Healing Diabetic Ulcers of the Lower Limb: Systematic Review and Meta-Analysis

The Clinical and Economic Potential of Hyperbaric Oxygen Therapy in the Treatment of Diabetic Ulceration and Other Conditions

Selective use of systemic hyperbaric oxygen therapy (HBOT) is a treatment that deserves further study and analysis. The current situation in the United Kingdom (UK) is discussed in relation to available evidence and practices elsewhere. It would appear that there is increasing evidence that HBOT could benefit many patients and health care budgets through improved clinical efficacy and cost-efficiency in the treatment of specific conditions, notably nonhealing diabetic ulceration of the lower limbs. This is not only disabling, it may lead to amputation. It is also a financial burden to patients and health service providers. In the UK, it is estimated that chronic wound care costs more than pound1 billion a year, with diabetic ulceration accounting for a substantial part of that staggering sum. It has been said repeatedly, and quite correctly, that there is insufficient good-quality evidence upon which a properly informed decision may be made on the contribution HBOT might make to alleviate that situation. It is intriguing that no determined effort is apparent that would seek to settle the issue by encouraging and facilitating appropriately designed and conducted randomized controlled trials to assess the actual effects of this treatment. Indeed, a proposed government research initiative appears to have been cancelled. Is lack of research preventing provision of HBOT?

Angiogenesis and vasculogenesis: Inducing the growth of new blood vessels and wound healing by stimulation of bone marrow–derived progenitor cell mobilization and homing

During embryonic development, the vasculature is among the first organs to form and is in charge of maintaining metabolic homeostasis by supplying oxygen and nutrients and removing waste products. As one would expect, blood vessels are critical not only for organ growth in the embryo but also for repair of wounded tissue in the adult. An imbalance in angiogenesis (a time-honored term that globally refers to the growth of new blood vessels) contributes to the pathogenesis of numerous malignant, inflammatory, ischemic, infectious, immune, and wound-healing disorders. This review focuses on the central role of the growth of new blood vessels in ischemic and diabetic wound healing and defines the most current nomenclature that describes the neovascularization process in wounds. There are now two well-defined, distinct, yet interrelated processes for the formation of postnatal new blood vessels, angiogenesis, and vasculogenesis. Reviewed are recent new data on vasculogenesis that promise to advance the field of wound healing.

Diagnosis and Treatment of Diabetic Foot Infections

Diagnosis and Treatment of Diabetic Foot Infections

Topical oxygen as an adjunct to wound healing: a clinical case series

Background: Disrupted vasculature and high energy-demand to support processing and regeneration of wounded tissue are typical characteristics of a wound site. Oxygen delivery is a critical element for the healing of wounds. Clinical experience with adjunctive hyperbaric oxygen therapy in the treatment of chronic wounds have shown that wound hyperoxia increases wound granulation tissue formation and accelerates wound contraction and secondary closure. Nevertheless, the physiologic basis for this modality remains largely unknown. Also, systemic hyperbaric oxygen therapy is associated with risks related to oxygen toxicity. Topical oxygen therapy represents a less explored modality in wound care. The advantages of topical oxygen therapy include low cost, lack of systemic oxygen toxicity, and the ability to receive treatment at home, making the benefits of oxygen therapy available to a much larger population of patients. Materials and methods: Over 9 months, seven surgeons treated 58 wounds in 32 patients with topical oxygen with follow-up ranging from 1 to 8 months. The data presented herein is a retrospective analysis of the results we have achieved using topical oxygen on complex wounds. Results: Thirty-eight wounds in 15 patients healed while on topical oxygen. An additional five wounds in five patients had preoperative oxygen therapy; all wounds initially healed postoperatively. In two patients, wounds recurred post-healing. In ten wounds, topical oxygen had no effect; and two of those patients went on to require limb amputation. There were no complications attributable to topical oxygen. Three patients died during therapy and one died in the first postoperative month from underlying medical problems. Two patients were lost to follow-up. Conclusions: In this case series, topical oxygen had no detrimental effects on wounds and showed beneficial indications in promoting wound healing.

Systematic reviews of wound care management: (3) antimicrobial agents for chronic wounds; (4) diabetic foot ulceration

Chronic wounds, including pressure sores, leg ulcers, diabetic foot ulcers and other kinds of wounds, healing by secondary intention are common in both acute and community settings. The prevention and treatment of chronic wounds includes many strategies, including the use of various wound dressings, bandages, antimicrobial agents, footwear, physical therapies and educational strategies. This review is one of a series of reviews, and focuses on the prevention and treatment of diabetic foot ulcers and the role of antimicrobial agents in chronic wounds in general. To assess the clinical- and cost-effectiveness of (1) prevention and treatment strategies for diabetic foot ulcers and (2) systemic and topical antimicrobial agents in the prevention and healing of chronic wounds. METHODS - DATA SOURCES: Nineteen electronic databases were searched, including MEDLINE, CINAHL, Embase and the Cochrane Library. Relevant journals, conference proceedings and bibliographies of retrieved papers were hand-searched. An expert panel was consulted. Randomised and non-randomised trials with a concurrent control group, which evaluated any intervention for the prevention or treatment of diabetic foot ulcers, or systemic or topical antimicrobials for chronic wounds (diabetic foot ulcers, pressure ulcers, leg ulcers of various aetiologies, pilonidal sinuses, non-healing surgical wounds, and cavity wounds) and used objective measures of outcome such as: (1) development or resolution of callus; (2) incidence of ulceration (for diabetic foot ulcer prevention studies); (3) incidence of pressure sores (pressure sore prevention studies); (4) any objective measure of wound healing (frequency of complete healing, change in wound size, time to healing, rate of healing); (5) ulcer recurrence rates; (6) side-effects; (7) amputation rates (diabetic foot ulcer treatment studies); (8) healing rates and recurrence of disease, among others, for pilonidal sinuses. Studies reporting solely microbiological outcomes were excluded. Decisions on the inclusion of primary studies were made independently by two reviewers. Disagreements were resolved through discussion. Data were extracted by one reviewer into structured summary tables. Data extraction was checked independently by a second reviewer and discrepancies resolved by discussion. All included studies were assessed against a comprehensive checklist for methodological quality. INCLUDED STUDIES - DIABETIC FOOT ULCERS: Thirty-nine trials which evaluated various prevention and treatment modalities for diabetic foot ulcers: footwear (2), hosiery (1), education (5), screening and foot protection programme (1); podiatry (1) for the prevention of diabetic foot ulcers; and footwear (1), skin replacement (2), hyperbaric oxygen (2), ketanserin (3), prostaglandins (3), growth factors (5), dressings and topical applications (9), debridement (2) and antibiotics (2) for the treatment of diabetic foot ulcers. INCLUDED STUDIES - ANTIMICROBIALS: Thirty studies were included, 25 with a randomised design. There were nine evaluations of systemic antimicrobials and 21 of topical agents. The methodological and reporting quality was generally poor. Commonly encountered problems of reporting included lack of clarity about randomisation and outcome measurement procedures, and lack of baseline descriptive data. Common methodological weaknesses included: lack of blinded outcome assessment and lack of adjustment for baseline differences in important variables such as wound size; large loss to follow-up; and no intention-to-treat analysis. RESULTS - PREVENTION OF DIABETIC FOOT ULCERS: There is some evidence (1 large trial) that a screening and foot protection programme reduces the rate of major amputations. The evidence for special footwear (2 small trials) and educational programmes (5 trials) is equivocal. A single trial of podiatric care reported a significantly greater reduction in callus in patients receiving podiatric care. RESULTS - TREATMENT OF DIABETIC FOOT ULCERS: Total contact casting healed significantly more ulcers than did standard treatment in one study. There is evidence from 5 trials of topical growth factors to suggest that these, particularly platelet-derived growth factor, may increase the healing rate of diabetic foot ulcers. Although these studies were of relatively good quality, the sample sizes were far too small to make any definitive conclusions, and growth factors should be compared with current standard treatments in large, multicentre studies. Topical ketanserin increased ulcer healing rate in 2 studies, while systemic hyperbaric oxygen therapy reduced the rate of major amputations in 1 study. Preliminary research into the effects of iloprost and prostaglandin E1 (PGE1) on diabetic foot ulcer healing suggests possible benefits. However, good quality, large-scale confirmatory research is needed. (ABSTRACT TRUNCATED)

Systemic hyperbaric oxygen therapy: lower-extremity wound healing and the diabetic foot.

To document peer-reviewed medical publications that have reported on hyperbaric oxygen (HBO) therapy as an adjunct to standard lower-extremity wound care, focusing on publications dealing with the diabetic foot. A review of the medical literature was conducted using MEDLINE. Research articles involving HBO treatment and the diabetic foot were critiqued to identify factors that may have been a source of bias. Of the published reports on human studies, seven involved diabetes-related foot pathology. Five of these studies, two of which were randomized, included a control group that did not receive HBO therapy The controlled diabetic foot studies included an average of 28 subjects in the HBO therapy group (range 10-62) and an average of 16.2 subjects in the non-HBO control group (range 5-33). Most of the published reports have several potential sources of bias, including, but not limited to, inadequate evaluation of comorbid conditions relevant to wound healing, small sample size, and poor documentation of wound size or severity. Four of the seven reports involving the diabetic foot were published by a group of researchers at the University of Milan between 1987 and 1996. Additional randomized placebo-controlled clinical trials in large diabetic populations would further lend credence to the presumption that HBO therapy improves clinical outcomes. Given the relatively high cost of this treatment modality, perhaps a more acute awareness of the medical literature would reduce the economic burden that HBO therapy imposes on care providers that are financially at risk.

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.

Topical Hyperbaric Therapy for Problem Skin Wounds

Hyperbaric oxygen remains the sole treatment capable of inducing growth of new blood vessels. However, systemic hyperbaric oxygen therapy risks central nervous system and pulmonary toxicity. To describe topical hyperbaric oxygen therapy for the treatment of recalcitrant open wounds. Topical and systemic hyperbaric oxygen treatments are described and contrasted from one another. Applications of topical hyperbaric oxygen therapy are described. Topical hyperbaric oxygen therapy is useful only for open wounds. The advantages of topical hyperbaric oxygen therapy include low cost, the lack of systemic oxygen toxicity, and effectiveness, allowing this treatment to be prescribed for many patients early in the course of their disease rather than as a last resort.