Folke Lind

Hyperbaric oxygen (HBO) therapy in treatment of diabetic foot ulcers. Long-term follow-up

BACKGROUND The cause of diabetic foot ulcers is multifactorial, e.g., neuropathy and angiopathy, leading to functional disturbances in the macrocirculation and skin microcirculation. Adequate tissue oxygen tension is an essential factor in infection control and wound healing. Hyperbaric oxygen (HBO) therapy, daily sessions of oxygen breathing at 2.5-bar increased pressure in a hyperbaric chamber, has beneficial actions on wound healing including antimicrobial action, prevention of edema and stimulation of fibroblasts. The aim of the present study was to investigate the long-term effect of HBO in treatment of diabetic foot ulcers. METHODS Thirty-eight diabetic patients (30 males) with chronic foot ulcers were investigated in a prospective study. The mean age was 60+/-13 years and the mean diabetes duration 27+/-14 years. All patients were evaluated with measurements of transcutaneous oxygen tension (tcPO(2)), peripheral blood pressure, and HbA(1c). All patients had a basal tcPO(2) value lower than 40 mmHg, which increased to >/=100 mmHg, or at least three times the basic value, during inhalation of pure oxygen. Seventeen patients underwent 40-60 sessions of HBO therapy, while 21 patients were treated conventionally. The follow-up time was 3 years. RESULTS 76% of the patients treated with HBO (Group A) had healed with intact skin at a follow-up time of 3 years. The corresponding value for patients treated conventionally (Group B) was 48%. Seven patients (33%) in Group B compared to two patients (12%) in Group A went to amputation. Peripheral blood pressure, HbA(1c), diabetes duration, and basal values of tcPO(2) were similar in both groups. CONCLUSIONS Adjunctive HBO therapy can be valuable for treating selected cases of hypoxic diabetic foot ulcers. It seems to accelerate the rate of healing, reduce the need for amputation, and increase the number of wounds that are completely healed on long-term follow-up. Additional studies are needed to further define the role of HBO, as part of a multidisciplinary program, to preserve a functional extremity, and reduce the short- and long-term costs of amputation and disability.

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.

HYPERBARIC OXYGEN THERAPY FOR WOUND COMPLICATIONS AFTER SURGERY IN THE IRRADIATED HEAD AND NECK: A REVIEW OF THE LITERATURE AND A REPORT OF 15 CONSECUTIVE PATIENTS

Radiotherapy, which is often used for cancer in the head and neck, leads to damage of tissue cells and vasculature. Surgery in such tissues has an increased complication rate, because wound healing requires angiogenesis and fibroplasia as well as white blood cell activity, all of which are jeopardized. Hyperbaric oxygen therapy (HBO) raises oxygen levels in hypoxic tissue, stimulates angiogenesis and fibroplasia, and has antibacterial effects.

Hyperbaric Oxygen Treatment of Active Cluster Headache: A Double-Blind Placebo-Controlled Cross-Over Study

Sixteen patients, 12 with episodic and four with chronic cluster headache (CH) according to the International Headache Society criteria (1), participated in the study. They were randomly selected to start with one out of two different hyperbaric treatments in a double-blind, placebo-controlled, cross-over study design. Both gases were administered by mask inside a multiplace hyperbaric chamber for 70 min at 250 kPa (2.5 ATA) in two sessions 24 h apart. Active treatment was 100% oxygen (HBO treatment), while placebo treatment was 10% oxygen in nitrogen (hyperbaric normoxic placebo = sham treatment) corresponding to breathing air at sea level. All patients were decompressed on air. The patients documented the number of headache attacks and their degree of severity according to a modified VAS scale (level 0-4, where level 0 = no headache and level 4 = very severe headache). A headache index (HI = sum of (number of attacks times degree of severity)) was calculated for the run-in week prior to and the week after each separate treatment. A treatment was regarded as effective if it reduced the HI by > 50%. Blood samples were taken from the external jugular vein before and during hyperbaric treatment (after 30 and 70 min), 1 day and 1 week after each treatment for analyses of calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY) and in a few patients also endotheline and nitrate. No difference between HBO and sham treatment on the HI or the prophylactic effect was observed in our study. However, 83% of the episodic CH patients and 25% of the chronic ones responded to either of the two treatments with at least 50% reduction of HI or remission for shorter or longer periods. This response rate exceeds an expected high placebo response due to the study procedure. Two episodic CH patients still experienced remission on follow-up 1 year after sham treatment. Five patients reported mild or moderate CH attacks during the sham treatment, and none during the HBO treatment. Changes in neuropeptides, endotheline and nitrate levels did not differ systematically when comparing the two different hyperbaric treatments or with respect to responders and non-responders. We conclude that two HBO sessions were not more effective than two sham treatments in reducing the HI and interrupting the CH period when given in a well-established cluster period or in chronic CH. The hyperbaric condition itself seems effective in reducing the HI, at least in patients with episodic CH, although a powerful placebo response can not be ruled out.

Hyperbaric Oxygen Treatment of Postoperative Neurosurgical Infections

OBJECTIVE To evaluate the clinical usefulness of hyperbaric oxygen (HBO) therapy for neurosurgical infections after craniotomy or laminectomy. METHODS The study involved review of medical records, office visits, and telephone contacts for 39 consecutive patients who were referred in 1996 to 2000. Infection control and healing without removal of bone flaps or foreign material, with a minimum of 6 months of follow-up monitoring, were considered to represent success. RESULTS Successful results were achieved for 27 of 36 patients, with a mean follow-up period of 27 months (range,6-58 mo). One patient discontinued HBO therapy because of claustrophobia, and two could not be evaluated because of death resulting from tumor recurrence. In Group 1 (uncomplicated cranial wound infections), 12 of 15 patients achieved healing with retention of bone flaps. In Group 2 (complicated cranial wound infections, with risk factors such as malignancy, radiation injury, repeated surgery, or implants), all except one infection resolved; three of four bone flaps and three of six acrylic cranioplasties could be retained. In Group 3 (spinal wound infections), all infections resolved, five of seven without removal of fixation systems. There were no major side effects of HBO treatment. CONCLUSION HBO treatment is an alternative to standard surgical removal of infected bone flaps and is particularly useful in complex situations. It can improve outcomes, reduce the need for reoperations, and allow infection control without mandatory removal of foreign material. HBO therapy is a safe, powerful treatment for postoperative cranial and spinal wound infections, it seems cost-effective, and it should be included in the neurosurgical armamentarium.

Hyperbaric oxygen therapy activates hypoxia-inducible factor 1 (HIF-1), which contributes to improved wound healing in diabetic mice

Hyperbaric oxygen (HBO) therapy has been used as an adjunctive therapy for diabetic foot ulcers, although its mechanism of action is not completely understood. Recently, it has been shown that HBO mobilizes the endothelial progenitor cells (EPCs) from bone marrow that eventually will aggregate in the wound. However, the gathering of the EPCs in diabetic wounds is impaired because of the decreased levels of local stromal‐derived factor‐1α (SDF‐1α). Therefore, we investigated the influence of HBO on hypoxia‐inducible factor 1 (HIF‐1), which is a central regulator of SDF‐1α and is down‐regulated in diabetic wounds. The effects of HBO on HIF‐1α function were studied in human dermal fibroblasts, SKRC7 cells, and HIF‐1α knock‐out and wild‐type mouse embryonic fibroblasts using appropriate techniques (Western blot, quantitative polymerase chain reaction, and luciferase hypoxia‐responsive element reporter assay). Cellular proliferation was assessed using H3‐thymidine incorporation assay. The effect of HIF in combination with HBOT was tested by inoculating stable HIF‐1α‐expressing adenovirus (Adv‐HIF) into experimental wounds in db/db mice exposed to HBO. HBO activates HIF‐1α at several levels by increasing both HIF‐1α stability (by a non‐canonical mechanism) and activity (as shown both by induction of relevant target genes and by a specific reporter assay). HIF‐1α induction has important biological relevance because the induction of fibroblast proliferation in HBO disappears when HIF‐1α is knocked down. Moreover, the local transfer of stable HIF‐1α‐expressing adenovirus (Adv‐HIF) into experimental wounds in diabetic (db/db mice) animals has an additive effect on HBO‐mediated improvements in wound healing. In conclusion, HBO stabilizes and activates HIF‐1, which contributes to increased cellular proliferation. In diabetic animals, the local transfer of active HIF further improves the effects of HBO on wound healing.

Necrotizing fasciitis following transobturator tape treated by extensive surgery and hyperbaric oxygen

The transobturator sling procedure (TVT-O) was developed to minimize surgical risks involved in treating genuine stress incontinence. All data suggest that most risks associated with the retropubic route such as injuries to the bladder, intestines or vessels are practically obsolete with the obturator route. However, severe soft-tissue infections have been reported with this new technique. In this case report, necrotizing fasciitis (NF) developed shortly after a TVT-O procedure. This life-threatening complication required extensive debridements, a diverting colostomy, antibiotics, and eight sessions of hyperbaric oxygen (HBO) therapy. We emphasize the importance of a unified interdisciplinary clinical approach in severe NF with rapid progression and systemic toxemia. Primary, aggressive but tissue-saving debridements together with antibiotics are the cornerstones of therapy. HBO therapy can oxygenate infected hypoxic tissues to help marginally viable tissues survive, reduce the inflammatory response, improve leukocyte bacterial oxidative killing capacity, and achieve infection control and healing.

Impact of acute hypobaric hypoxia on blood flow distribution in brain

Aim:  Acute hypobaric hypoxia is well known to alter brain circulation and to cause neuropsychological impairment. However, very few studies have examined the regional changes occurring in the brain during acute exposure to extreme hypoxic conditions.

Hyperbaric Oxygen in Lower Limb Trauma (HOLLT); protocol for a randomised controlled trial.

Introduction Open fractures with significant soft tissue injury are associated with high rates of complications, such as non-union, infection, chronic pain and disability. Complications often require further inpatient care, and in many cases, multiple operations and prolonged rehabilitation. Use of hyperbaric oxygen therapy as an adjunct to standard orthopaedic trauma care has the potential to reduce the complications of musculoskeletal injury and thus improve outcomes. Two previous randomised trials have suggested some positive effect, but neither functional measures nor long-term outcomes were reported. Methods and analysis An international, multicentre, randomised, open-label, clinical trial. Patients with trauma with an acute open fracture of the tibia with severe soft tissue injury (Gustilo grade 3) and high risk of injury-related complications were recruited from participating major trauma hospitals with hyperbaric facilities. Patients were enrolled with the expectation of commencing 12 sessions of hyperbaric oxygen therapy within 48 h of injury. The primary outcome measure is the incidence of acute complications of the open fracture wound at 14 days. Other short-term outcome measures include amputation, need for fasciotomy, time until wound closure, breakdown of closed wounds, time until definitive orthopaedic fixation, number of operative procedures, intensive care stay and hospital stay. Long-term follow-up will continue for 2 years postinjury. Ethics and dissemination Ethics approval was given by The Alfred Health Human Ethics Committee (206/04) and the Monash University Human Research Ethics Committee (CF07/4208). Approval was also obtained from the institutional research ethics committee at each participating site. This study will make a significant contribution to the trauma literature and should answer the question of whether hyperbaric oxygen therapy can significantly improve outcomes in severe lower limb trauma. Collective study results will be published in international journals and presented at relevant conferences. Trial registration number Clinicaltrials.gov: NCT00264511; Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12607000559415.

Comparison between near-infrared oximetry and 99mTc-HMPAO uptake in the resting peripheral muscle under normobaric normoxia and hypobaric hypoxia

We have used three different oximeters to study finger capillary SatO2, transcutaneous oxygen tension and vastus lateralis hemoglobin saturation and hemoglobin concentration in 6 volunteers under normobaric normoxia and hypobaric hypoxia. Simultaneously, the 99mTc-HMPAO uptake in the thigh muscles was assessed by planar scintigraphy. We found a highly selective uptake of 99mTc-HMPAO in the muscles of all subjects thighs. 99mTc-HMPAO uptake was significantly higher in hypoxia as compared to normoxia (p < 0.001). By comparing scintigraphy and tissue spectrophotometry (OMNIA), we observed a strong correlation between 99mTc-HMPAO uptake and hemoglobin saturation (R equals 0.96, p < 0.001) and a good correlation between 99mTc-HMPAO uptake and hemoglobin concentration (R equals 0.77, p < 0.05). These correlations indicate the occurrence of a protective vasodilatory response during hypobaric hypoxia. During hypoxia, none of the three methods used to measure oxygen saturation correlated with the actual arterial SatO2. This results suggest that different body districts react to hypoxia in a non-uniform manner. The role of the used NIRS instrumentation in assessing quantitative values needs further investigations.