The Undersea and Hyperbaric Medical Society issued the following policy statement on topical oxygen, often referred to as "topical hyperbaric oxygen therapy" (Feldmeier et al, 2005): "1. Topical oxygen should not be termed hyperbaric oxygen since doing so either intentionally or unintentionally suggests that topical oxygen treatment is equivalent or even identical to hyperbaric oxygen. Published documents reporting experience with topical oxygen should clearly state that topical oxygen not hyperbaric oxygen is being employed. 2. Mechanisms of action or clinical study results for hyperbaric oxygen cannot and should not be co-opted to support topical oxygen since hyperbaric oxygen therapy and topical oxygen have different routes and probably efficiencies of entry into the wound and their physiology and biochemistry are necessarily different. 3. The application of topical oxygen cannot be recommended outside of a clinical trial at this time based on the volume and quality of scientific supporting evidence available, nor does the Society recommend third party payor reimbursement. 4. Before topical oxygen can be recommended as therapy for non-healing wounds, its application should be subjected to the same intense scientific scrutiny to which systemic hyperbaric oxygen has been held".
Limb-specific TOT entails sealing an individual's arm or leg into an air-tight plastic container that is sealed with pliable gaskets, and exposing the limb to pure oxygen greater than 1 atm of pressure. Much of the research on this form of therapy has centered on chronic wounds arising in individuals with diabetic foot ulcers (DFUs). However, there is currently insufficient evidence from Routine Clinical Trials (RCTs) to determine the effectiveness of limb-specific TOT.
In 2008, Banks et al. examined the effectiveness of the EPIFLO® device as an adjunct treatment modality in chronic wound management. This study included 3 men with spinal cord injury (SCI), who each presented with a stage IV pressure ulcer in the pelvic region. They were treated with the EPIFLO® device as an adjunct therapy. In Case 1, the patient was monitored for 9 weeks, whereas in Cases 2 and 3, the patients were monitored for 5 weeks. Healing was determined on a weekly basis by wound dimensions and volume, which were compared before and after the intervention. Comparison of pre- and post-treatment outcome measurements showed significant improvement with EPIFLO® in each case. The authors concluded that EPIFLO® seems to have had a positive effect on the healing rate of chronic pressure ulcers in individuals with SCI. The findings of this small case-series study need to be validated by well-designed studies.
In 2008, Bakri et al. tested the hypothesis that local transdermal delivery of oxygen improves oxygenation in sternotomy wounds after cardiac surgery; the secondary hypothesis was that supplemental inspired oxygen improves sternal wound PsqO(2). After undergoing cardiopulmonary bypass, a total of 30 patients randomly received EPIFLO® oxygen generators that provided oxygen at 6 ml/hr into an occlusive wound dressing, or identical-appearing inactive generators. PsqO(2) and temperature were measured in the wound approximately 5-mm below the skin surface. PsqO(2) and arterial oxygen (Pao(2)) were measured 1 hr after intensive care unit admission (Fio(2) = 60%) and on the 1st and 2nd post-operative mornings at Fio(2) of both 30% and 50% in random order. Data from 4 patients were excluded for technical reasons. Patient characteristics were similar in each group, as were type of surgery and peri-operative management. Increasing Fio(2) from 30% to 50% improved Pao(2) from 99 [84 to 116] to 149 [128 to 174] mm Hg (p < 0.001, mean [95% CI]) and sternal wound PsqO(2) from 23 [16 to 33] to 27 [19 to 38] mm Hg (p < 0.001). In contrast, local oxygen delivery did not improve tissue oxygenation: 24 [14 to 41] versus 25 [16 to 41] mm Hg (p = 0.88). The authors concluded that additional inspired oxygen improved Pao(2) and sternal wound PsqO(2) after cardiopulmonary bypass surgery, and may, consequently, reduce infection risk. However, oxygen insufflated locally into an occlusive dressing did not improve wound PsqO(2) and, therefore, does not appear to be useful clinically in cardiac surgery patients to reduce sternal wound infections.
In 2017, Purvis et al. performed a retrospective chart review of records collected between January 1, 2007, and July 18, 2016, from male and female patients ranging in age from 4 years to 105 years. All wounds were at least 1 cm2 and were treated with at least 1 separate modality before treatment with GWR Medical’s single-use, disposable O2Boot®or O2Sacral® device, and then treated with O2Boot® or O2Sacral® device for a minimum of 2 weeks in compliance with the FDA-approved indications. The treatment was associated with an overall rate of 59.4% for a reduction in chronic wound size, while 41.6% of wounds had no healing. The overall amputation rate was 2.4% for wounds in this study.
In 2009, Gordillo et al. reviewed the evidence including in vitro, preclinical data and clinical data regarding the use of TOT in the treatment of lower extremity wounds. Randomized controlled trials are not yet reported and clearly necessary. The authors concluded the current body of evidence suggests that TOT may be considered as a second line of therapy for refractory wounds.
In 2010, Schreml et al. noted that oxygen is a pre-requisite for successful wound healing due to the increased demand for reparative processes, such as cell proliferation, bacterial defense, angiogenesis and collagen synthesis. The author stated that even though the role of oxygen in wound healing is not yet completely understood, many experimental and clinical observations have shown wound healing to be impaired under hypoxia. However, this review did not provide any clinical data to support the use of TCOT for wound healing.
In 2010, Blackman et al. examined the clinical efficacy of a pressurized topical oxygen therapy (TWO(2)) device in outpatients (n = 28) with severe DFUs referred for care to a community wound care clinic, and evaluated ulcer reoccurrence rates after 24 months. A total of 17 patients received TWO(2) 5 times per week (60-min treatment, pressure cycles between 5 and 50 mb) and 11 selected a silver-containing dressing changed at least twice per week (control). Patient demographics did not differ between treatment groups, but wounds in the treatment group were more severe, perhaps as a result of selection bias. Ulcer duration was longer in the treatment (mean of 6.1 months, SD 5.8) than in the control group (mean of 3.2 months, SD 0.4) and mean baseline wound area was 4.1 cm2 (SD 4.3) in the treatment and 1.4 cm2 (SD 0.6) in the control group (p = 0.02). Fourteen of 17 ulcers (82.4 %) in the treatment group and 5 of 11 ulcers (45.5 %) in the control group healed after a median of 56 and 93 days, respectively (p = 0.04). No adverse events were observed and there was no re-occurrence at the ulcer site after 24 months' follow-up in either group. The authors noted that although the absence of randomization and blinding may have under- or over-estimated the treatment effect of either group, the significant differences in treatment outcomes confirmed the potential benefits of TWO(2) in the management of difficult-to-heal DFUs. Moreover, they stated that clinical efficacy and cost-effectiveness studies, as well as, studies to elucidate the mechanisms of action of TWO(2) are needed.
In 2012, Woo et al. evaluated the effectiveness of TCOT on chronic wound healing in 9 patients. After 4 weeks of treatment, mean wound surface area and wound infection check-list scores were significantly reduced. Signs of bacterial damage were also reduced. The authors concluded that findings from this study suggested TCOT may be beneficial in promoting chronic wound healing. These preliminary findings from a small pilot study need to be validated by well-designed studies.
In 2014, Brannick et al. evaluated the diagnostic workup and treatment of a patient with a history of venous insufficiency and a large, painful non-healing ulcer and the use of CDO therapy to facilitate healing. This case study involved a 53 year old female. The initial lower extremity physical exam revealed lower extremity hyperpigmentation and hemosiderin deposition in the bilateral gaiter area. Full thickness ulceration to the level of the dermis was present in the medial right ankle at the level of the medial malleolus. The ulcer measured 6.7 cm x 5.3 cm. Hypergranulation tissue was present at the wound base. The wound was well circumscribed and irregularly shaped with erythematous borders. Active serous drainage was present. There was no odor, no purulence and no gross signs of infection. CDO therapy as a treatment modality was implemented using TransCu O2® (EO2) concepts at 10ml/hr followed by a 4 layer compression dressing. The patient’s ulcer pain ranged from 3/10 to 8/10 on the visual analog scale (VAS) throughout the 5 month duration of the ulcer, requiring the patient to take pain medications when needed. The patient reported a pain level of only 2/10 after 20 days of CDO treatment and did not need additional pain medication at that time. At the 20 day mark, the CDO therapy was temporarily discontinued, as the patient was leaving town for a holiday. The patient returned to the clinic six days later (day 26 since beginning continuous therapy) and related 10/10 pain and difficulty sleeping. CDO treatment was resumed. Three days after restarting the therapy, the patient demonstrated adequate pain control and discontinued taking narcotic pain medications. The wound measurements taken at day 54 of treatment were 3.6 cm x 1.3 cm with mild hypergranulation. Complete wound closure occurred in 79 days with 100% epithelialization over the hypergranulation tissue. The authors concluded the treatment and management of chronic wounds can often be challenging. Oxygen is necessary for both cellular metabolism and host defense. CDO is capable of delivering continuous oxygen without pressure and at a low flow rate to a chronic wound. In addition, this device does not compromise the normal dressings or patient mobility. This case study concludes that it demonstrates a successful use of CDO in healing a chronic painful large wound. However, causality cannot be concluded from this study, therefore, randomized controlled trials are needed to assess the effectiveness of this therapy.
In 2015, Niederauer et al. assessed the use of CDO therapy to sham therapy in the treatment of DFUs in a prospective randomized double-blind multicenter study. One hundred subjects were enrolled and randomized with DFUs, 79% male aged 58.3 +/- 12.1 years were to receive either active CDO therapy using an active CDO device, or an otherwise fully operational sham device that provided moist wound therapy (MWT) without delivering oxygen. Patients were followed to closure or 12 weeks, whichever was sooner. Patients, treating physicians and independent evaluators were blinded to the study arm. All patients received identical offloading, dressings and follow-up. There were no significant differences in assessed descriptive characteristics between the treatment arms (P>0.5 for all). A significantly higher proportion of people healed in the active arm compared to sham (46% vs 22%, P = 0.02). This relative effect became greater in more chronic wounds (42.5% vs 13.5%, P = 0.006). Patients randomized to the active device experienced significantly faster rates of closure relative to the sham (P < 0.001). The authors concluded a significantly greater percentage and rate of healing in patients receiving CDO therapy compared to a sham device providing standard wound therapy. The study revealed that CDO therapy appears to have a similar or greater effect as the wound size increases. Furthermore, the relative effect of CDO therapy on more chronic wounds appears to be more pronounced as the wounds become more chronic. These results appear to indicate that the with more chronicity and size, the greater the apparent effect. We look forward to further works that may confirm or build on these data.