INTRODUCTION:Hyperbaric oxygen treatment (HBOT) is sometimes used in the management of open fractures and severe soft tissue crush injury, aiming to reduce complications and improve outcomes.METHODS:Patients with open tibial fractures were randomly assigned within 48 hours of injury to receive standard trauma care or standard care plus 12 sessions of HBOT. The primary outcome was the incidence of necrosis or infection or both occurring within 14 days of injury.RESULTS:One-hundred and twenty patients were enrolled. Intention to treat primary outcome occurred in 25/58 HBOT assigned patients and 34/59 controls (43% vs 58%, odds ratio (OR) 0.55, 95% confidence interval (CI) 0.25 to 1.18, P = 0.12). Tissue necrosis occurred in 29% of HBOT patients and 53% of controls (OR 0.35, 95% CI 0.16 to 0.78, P = 0.01). There were fewer late complications in patients receiving HBOT (6/53 vs 18/52, OR 0.22, 95% CI 0.08 to 0.64, P = 0.007) including delayed fracture union (5/53 vs 13/52, OR 0.31, 95% CI 0.10 to 0.95, P = 0.04). Quality of life measures at one and two years were superior in HBOT patients. The mean score difference in short form 36 was 2.90, 95% CI 1.03 to 4.77, P = 0.002, in the short musculoskeletal function assessment (SMFA) was 2.54, 95% CI 0.62 to 4.46, P = 0.01; and in SMFA daily activities was 19.51, 95% CI 0.06 to 21.08, P = 0.05.CONCLUSIONS:In severe lower limb trauma, early HBOT reduces tissue necrosis and the likelihood of long-term complications, and improves functional outcomes. Future research should focus on optimal dosage and whether HBOT has benefits for other injury types.

Background Late radiation cystitis is an adverse effect of cancer treatment with radiotherapy in the pelvic region. Symptoms of late radiation cystitis can be assessed with the Expanded Prostate Index Composite Score (EPIC). Previous reports indicate that hyperbaric oxygen therapy reduces symptoms from late radiation cystitis, but the evidence is predominantly based on non-randomised and retrospective studies. We aimed to assess whether hyperbaric oxygen therapy would mitigate symptoms of late radiation cystitis. Methods We did a randomised, controlled, phase 2-3 trial (RICH-ART [Radiation Induced Cystitis treated with Hyperbaric oxygen-A Randomised controlled Trial]) at five Nordic university hospitals. All patients aged 18-80 years, with pelvic radiotherapy completed at least 6 months previously, a score of less than 80 in the urinary domain of the Expanded Prostate Index Composite Score (EPIC), and referred to participating hyperbaric clinics due to symptoms of late radiation cystitis, were eligible for inclusion. Exclusion criteria were ongoing bleeding requiring blood transfusion exceeding 500 mL in the past 4 weeks, permanent urinary catheter, bladder capacity less than 100 mL, fistula in the urinary bladder, previous treatment with hyperbaric oxygen therapy for late radiation injuries, and contraindications to hyperbaric oxygen therapy. After computer-generated 1:1 randomisation with block sizes of four for each stratification group (sex, time from radiotherapy to inclusion, and previous invasive surgery in the pelvic area), patients received hyperbaric oxygen therapy (30-40 sessions, 100% oxygen, breathed at a pressure of 240-250 kPa, for 80-90 min daily) or standard care with no restrictions for other medications or interventions. No masking was applied. The primary outcome was change in patient-perceived urinary symptoms assessed with EPIC from inclusion to follow-up at visit 4 (6-8 months later), measured as absolute change in EPIC urinary total score. RICH-ART closed enrolment on Dec 31, 2017; the last follow-up data will be compiled in 2023. RICH-ART is registered with ClinicalTrials.gov, number NCT01659723, and with the European Medicines Agency, number EudraCT 2012-001381-15. Findings Of 223 patients screened between May 9, 2012, and Dec 20, 2017, 87 patients were enrolled and randomly assigned to either hyperbaric oxygen therapy (n=42) or standard care (n=45). After excluding eight patients who withdrew consent directly after randomisation (one in the hyperbaric oxygen therapy group and seven in the standard care group), 79 were included in the intention-to-treat analyses (n=41 in the hyperbaric oxygen therapy group, n=38 in the standard care group). Median time from randomisation to visit 4 was 234 days (IQR 210-262) in the hyperbaric oxygen therapy group and 217 days (195-237) in the standard care group. The difference between change in group mean of EPIC urinary total score at visit 4 was 10.1 points (95% CI 2.2-18.1; p=0.013; 17.8 points [SD 18.4] in the hyperbaric oxygen therapy group vs 7.7 points [15.5] in the standard care group). 17 (41%) of 41 patients in the hyperbaric oxygen therapy group experienced transient grade 1-2 adverse events, related to sight and hearing, during the period of hyperbaric oxygen therapy. Interpretation Our results suggest that hyperbaric oxygen therapy relieves symptoms of late radiation cystitis. We conclude that hyperbaric oxygen therapy is a safe and well tolerated treatment.

Background: In neuromodulation therapies, hardware-related infections are a major challenge often leading to hardware removal. Objective: To investigate the role of adjuvant hyperbaric oxygen therapy (HBOT) in hardware-related infections. Methods: Fourteen hardware-related infection events in 12 consecutive patients between 2002 and 2015 were treated with antibiotics and adjuvant HBOT at the Karolinska University Hospital (Stockholm, Sweden). Two time-independent infection events related to hardware replacements occurred in 2 patients. Infection resolution and the need for hardware removal were assessed. Results: Twelve out of 14 events of hardware-related infection were successfully treated without hardware removal (86%). The 2 patients treated twice with HBOT on 2 time-independent occasions could retain their hardware in both cases. Hardware was removed following HBOT failure in 2 infection events, with long-term infection control achieved in all patients. Further, an intrathecal pump malfunction caused by HBOT at 2.8 bars was observed, leading to a change in the manufacturer’s guidelines. Conclusions: This study indicates a potential benefit of adjuvant HBOT in the treatment of hardware-related infections in neuromodulation, diminishing the need for hardware removal and treatment interruption. Prospective studies are warranted to establish the role of adjuvant HBOT in the treatment of hardware-related infections in neuromodulation.

There is a need to improve outcome in patients with brain abscesses and hyperbaric oxygen therapy (HBOT) is a promising treatment modality. The objective of this study was to evaluate HBOT in the treatment of intracranial abscesses.

BACKGROUND Deep decompression stops are increasingly common in recreational technical diving. Concerns exist that they shift decompression stress back into slower tissues. A diver recorded an exceptional exposure dive, with deeps stops, on a commercially available dive computer. MATERIAL AND METHODS Using the R package SCUBA tissue inert gas pressures in 17 Bühlmann (ZH-L16A) compartments were estimated from the dive computer recorded profile. The RGBM dive plan generated by the diver's software was similarly interrogated, as was a third profile with reduced deep stops generated using the VPM-B/E model. RESULTS In this dive the combination of 5 gas switches appeared to ameliorate the effect of deep stops from 76 m depth. CONCLUSIONS A higher-than-anticipated inert gas content in a decompression mixture, coupled with climbing 200 stairs post-decompression, appear possible risk factors for decompression sickness. Nonetheless, the physiological effect of deep decompression stops during exceptional exposure, even when diving with gas switches, remains urgently to be determined to improve safe decompression following exceptional exposures. Until algorithms utilising deep decompression stops are validated with human data, dive profiles incorporating deep decompression stops should be considered experimental.

Hyperbaric oxygen treatment (HBOT) of critically ill patients requires special technology and appropriately trained medical team staffing for '24/7' emergency services. Regardless of the chamber system used it is essential that the attending nurse and critical care specialist understand the physics and physiology of hyperbaric oxygen for safe treatment and compression/decompression procedures. Mechanical ventilation through endotracheal tube or tracheotomy is hampered by the increased gas density and flow resistance with risks of hypoventilation, carbon dioxide retention and oxygen seizures. Ventilation should be controlled and arterial and end-tidal carbon dioxide levels monitored. Haemodynamically unstable patients require careful risk-benefit evaluation, invasive monitoring and close supervision of inotropes, vasopressors and sedative drug infusions to avoid blood pressure swings and risk of awareness. Two distinctly different chambers are used for critical care. Small cost-efficient and easy-to-install acrylic monoplace chambers require less staffing and no inside attendant. Major disadvantages include patient isolation with difficulties to maintain standard organ support and invasive monitoring. Monoplace ventilators are less advanced and require the use of muscle relaxants and excessive sedation. Intravenous lines must be changed to specially designed IV pumps located outside the chamber with chamber pass-through and risk of inaccurate drug delivery. The multiplace chamber is better suited for HBOT of critically ill patients with failing vital functions and organ systems, primarily because it permits appropriate ICU equipment to be used inside the chamber by accompanying staff. Normal 'hands-on' intensive care continues during HBOT with close attention to all aspects of critical patient care. A regional trauma hospital-based rectangular chamber system immediately bordering critical care and emergency ward facilities is the best solution for safe HBOT in the critically ill. Disadvantages include long-term commitment, larger space requirements and higher capitalization, technical and staffing costs.

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.

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.

A patient data management system (PDMS) has been used for years in the intensive care unit (ICU) at the Karolinska University Hospital to provide bedside or remote clinical patient documentation and information. Data from monitors, mechanical ventilators and syringe pumps are fed into a central clinical information management system to monitor, display trends and record data of vital parameters, ventilator settings and drugs. In order to continue routine critical care monitoring and recording during hyperbaric oxygen therapy (HBOT), without endangering the safety demands of hyperbaric procedures, we have modified the PDMS system for hyperbaric use. Via an ethernet box placed inside the chamber, data are transmitted to the Clinisoft™ system through the local area network. By standardised risk-analysis procedures, in close cooperation between the hyperbaric and biomedical engineering departments, the chamber producer and the notifying body (Germanischer Lloyd), the ethernet box was modified to receive full safety approval by all parties. The PDMS is now functioning routinely during HBOT for intensive care patients so that data can be seen bedside and followed on-line in the ICU. Data are also continuously stored on the clinical information management system for later clinical or research purposes. Work continues to obtain CE approval for hyperbaric use for modern syringe pumps and mechanical ventilators connected to the PDMS system. Improved documentation of ICU care will improve quality of care during HBOT and facilitate research and development in hyperbaric medicine.

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.

Cervical necrotizing fasciitis is a serious, rapidly progressive infection along fascia planes that sometimes involves skin, subcutaneous tissue and muscle (myositis). The condition, often of dental or pharyngeal origin, is associated with high morbidity and mortality. Thirteen consecutive cases of cervical necrotizing fasciitis treated with hyperbaric oxygen at the Karolinska Hospital during the period 1997-2003 were reviewed. Eight male and five female patients, 33 to 78 years old, were treated according to the Karolinska Hospital guidelines for severe soft tissue infections. All patients recovered. Eleven of thirteen patients required intensive care and eight inotropic drugs. Streptococcus milleri was the predominant pathogen found in initial cultures. Three case reports are presented. Our findings lend further support to the literature on the importance of a prompt multidisciplinary approach with aggressive surgical intervention, broad-spectrum antibiotic therapy and hyperbaric oxygen therapy.

Background: Carbon monoxide (CO) poisoning can cause tissue injury. Neutrophil granulocytes have been proposed to contribute to the injury, which may be ameliorated by hyperbaric oxygen (HBO2) treatment. We sought to assess the relationship between acute CO poisoning and blood neutrophil count, plasma cytokine, and cortisol responses, as well as the mechanism behind the observed beneficiary effects of HBO2 treatment.Methods: Eight patients (age 26-82 years) with severe acute CO poisoning were enrolled, concomitant with eight healthy controls (age 27-42 years), in a prospective, controlled, clinical study. The patients were given three HBO2 treatments (2.8 atmospheres absolute, 100 minutes) within the first 24 hours. The controls were given identical simultaneous HBO2 treatments. Venous blood samples were taken before and after each treatment.Results: At the start of the HBo(2) treatment, patients displayed significantly higher blood neutrophil counts (p <.0001) and plasma cortisol levels (p = .020) than controls, but the two groups had similar values for interleukin-8, granulocyte colony-stimulating factor (G-CSF), neutrophil H2O2 generation, and CD16 and CD18 surface expression. During the observation time, neutrophil H2O2 accumulation declined in patients and in controls (p =.031), whereas the up-regulation of CD18 expression increased (p =.002) in both groups. Moreover, G-CSF levels became significantly higher in patients than in controls (p =.015). G-CSF levels also correlated significantly with neutrophil counts.Conclusion: CO poisoning was associated with discrete changes of blood neutrophil counts, cortisol, and G-CSF plasma concentrations. HBO2 treatment modulated neutrophil generation of H2O2 and surface expression of CD18. These changes may be part of the cascade of events leading to the sequelae of CO poisoning and their attenuation by HBO2.