Hyperbaric oxygen therapy compared to pharmacological intervention in fibromyalgia patients following traumatic brain injury: A randomized, controlled trial.

Fibromyalgia is a chronic pain syndrome with unsatisfactory response to current treatments. Physical trauma, including traumatic brain Injury (TBI) is among the etiological triggers. Hyperbaric Oxygen therapy (HBOT) is an intervention that combines 100% oxygen with elevated atmospheric pressure. HBOT has been applied as a neuro-modulatory treatment in central nervous system-related conditions. The current study investigated the utility of HBOT for TBI-related fibromyalgia. Fibromyalgia patients with a history of TBI were randomized to either HBOT or pharmacological intervention. HBOT protocol comprised 60 daily sessions, breathing 100% oxygen by mask at 2 absolute atmospheres (ATA) for 90 minutes. Pharmacological treatment included Pregabalin or Duloxetine. The primary outcome was subjective pain intensity on visual analogue scale (VAS); Secondary endpoints included questionnaires assessing fibromyalgia symptoms as well as Tc-99m-ECD SPECT brain imaging. Pain threshold and conditioned pain modulation (CPM) were also assessed. Results demonstrated a significant group-by-time interaction in pain intensity post-HBOT compared to the medication group (p = 0.001), with a large net effect size (d = -0.95) in pain intensity reduction following HBOT compared to medications. Fibromyalgia related symptoms and pain questionnaires demonstrated significant improvements induced by HBOT as well as improvements in quality of life and increase in pain thresholds and CPM. SPECT demonstrated significant group-by-time interactions between HBOT and medication groups in the left frontal and the right temporal cortex. In conclusion, HBOT can improve pain symptoms, quality of life, emotional and social function of patients suffering from FMS triggered by TBI. The beneficial clinical effect is correlated with increased brain activity in frontal and parietal regions, associated with executive function and emotional processing.

Hyperbaric oxygen therapy in children with post-concussion syndrome improves cognitive and behavioral function: a randomized controlled trial.

Persistent post-concussion syndrome (PPCS) is a common and significant morbidity among children following traumatic brain injury (TBI) and the evidence for effective PPCS treatments remains limited. Recent studies have shown the beneficial effects of hyperbaric oxygen therapy (HBOT) in PPCS adult patients. This randomized, sham-control, double blind trial evaluated the effect of hyperbaric oxygen therapy (HBOT) on children (age 8-15) suffering from PPCS from mild-moderate TBI events six months to 10 years prior. Twenty-five children were randomized to receive 60 daily sessions of HBOT (n = 15) or sham (n = 10) treatments. Following HBOT, there was a significant increase in cognitive function including the general cognitive score (d = 0.598, p = 0.01), memory (d = 0.480, p = 0.02), executive function (d = 0.739, p = 0.003), PPCS symptoms including emotional score (p = 0.04, d = - 0.676), behavioral symptoms including hyperactivity (d = 0.244, p = 0.03), global executive composite score (d = 0.528, p = 0.001), planning/organizing score (d = 1.09, p = 0.007). Clinical outcomes correlated with significant improvements in brain MRI microstructural changes in the insula, supramarginal, lingual, inferior frontal and fusiform gyri. The study suggests that HBOT improves both cognitive and behavioral function, PPCS symptoms, and quality of life in pediatric PPCS patients at the chronic stage, even years after injury. Additional data is needed to optimize the protocol and to characterize the children who can benefit the most.

Hyperbaric oxygen therapy improves neurocognitive functions and symptoms of post-COVID condition: randomized controlled trial.

Post-COVID-19 condition refers to a range of persisting physical, neurocognitive, and neuropsychological symptoms after SARS-CoV-2 infection. The mechanism can be related to brain tissue pathology caused by virus invasion or indirectly by neuroinflammation and hypercoagulability. This randomized, sham-control, double blind trial evaluated the effect of hyperbaric oxygen therapy (HBOT or HBO2 therapy) on post-COVID-19 patients with ongoing symptoms for at least 3 months after confirmed infection. Seventy-three patients were randomized to receive daily 40 session of HBOT (n = 37) or sham (n = 36). Follow-up assessments were performed at baseline and 1-3 weeks after the last treatment session. Following HBOT, there was a significant group-by-time interaction in global cognitive function, attention and executive function (d = 0.495, p = 0.038; d = 0.477, p = 0.04 and d = 0.463, p = 0.05 respectively). Significant improvement was also demonstrated in the energy domain (d = 0.522, p = 0.029), sleep (d = - 0.48, p = 0.042), psychiatric symptoms (d = 0.636, p = 0.008), and pain interference (d = 0.737, p = 0.001). Clinical outcomes were associated with significant improvement in brain MRI perfusion and microstructural changes in the supramarginal gyrus, left supplementary motor area, right insula, left frontal precentral gyrus, right middle frontal gyrus, and superior corona radiate. These results indicate that HBOT can induce neuroplasticity and improve cognitive, psychiatric, fatigue, sleep and pain symptoms of patients suffering from post-COVID-19 condition. HBOT's beneficial effect may be attributed to increased brain perfusion and neuroplasticity in regions associated with cognitive and emotional roles.

The effect of hyperbaric oxygen therapy on the pathophysiology of skin aging: a prospective clinical trial.

INTRODUCTION: Skin biopsies can be used to evaluate physiological effects of aging targeted intervention at the tissue/cellular levels. Recent clinical trials have shown that hyperbaric oxygen therapy (HBOT) can target aging hallmarks, including telomere shortening, senescent cells clearance and angiogenesis. The aim of this study was to evaluate the effects of HBOT on the skin of a normal, non-pathological, aging population. METHODS: The study was performed as a prospective clinical trial. After signing informed consent and undergoing baseline evaluations, the subjects were assigned to a three-month control period followed by three months of HBOT daily sessions. Skin biopsies were taken at baseline, after three months of no intervention (control) and 1-2 weeks following the last HBOT session. Trichrome, Orecin, lipofuscin and CD31 staining were used to evaluate collagen fibers, elastic fibers, senescent cells and blood vessels, respectively. RESULTS: Out of the cohort of 70 participants in the normal aging population study, thirteen male patients (age 68.07±2.5y) gave consent for repeated skin biopsies. Following HBOT, there was a significant increase in collagen density (p<0.001, effect size(es)=1.10), elastic fiber length (p<0.0001, es=2.71) and the number of blood vessels (p=0.02, es=1.00). There was a significant decrease in fiber fragmentation (p=0.012) and in tissue senescent cells (p=0.03, es=0.84) post-HBOT. No changes were noted in elastic fiber density or thickness. CONCLUSIONS: The study indicates, for the first time in humans, that HBOT can significantly modulate the pathophysiology of the skin aging in a healthy aging population. The demonstrated mechanisms include angiogenesis and senescent cell clearance.

Hyperbaric oxygen therapy increases telomere length and decreases immunosenescence in isolated blood cells: a prospective trial.

INTRODUCTION: Aging is characterized by the progressive loss of physiological capacity. At the cellular level, two key hallmarks of the aging process include telomere length (TL) shortening and cellular senescence. Repeated intermittent hyperoxic exposures, using certain hyperbaric oxygen therapy (HBOT) protocols, can induce regenerative effects which normally occur during hypoxia. The aim of the current study was to evaluate whether HBOT affects TL and senescent cell concentrations in a normal, non-pathological, aging adult population. METHODS: Thirty-five healthy independently living adults, aged 64 and older, were enrolled to receive 60 daily HBOT exposures. Whole blood samples were collected at baseline, at the 30th and 60th session, and 1-2 weeks following the last HBOT session. Peripheral blood mononuclear cells (PBMCs) telomeres length and senescence were assessed. RESULTS: Telomeres length of T helper, T cytotoxic, natural killer and B cells increased significantly by over 20% following HBOT. The most significant change was noticed in B cells which increased at the 30th session, 60th session and post HBOT by 25.68%±40.42 (p=0.007), 29.39%±23.39 (p=0.0001) and 37.63%±52.73 (p=0.007), respectively. There was a significant decrease in the number of senescent T helpers by -37.30%±33.04 post-HBOT (P<0.0001). T-cytotoxic senescent cell percentages decreased significantly by -10.96%±12.59 (p=0.0004) post-HBOT. In conclusion, the study indicates that HBOT may induce significant senolytic effects including significantly increasing telomere length and clearance of senescent cells in the aging populations.

Cognitive enhancement of healthy older adults using hyperbaric oxygen: a randomized controlled trial.

More than half of community-dwelling individuals sixty years and older express concern about declining cognitive abilities. The current study's aim was to evaluate hyperbaric oxygen therapy (HBOT) effect on cognitive functions in healthy aging adults.A randomized controlled clinical trial randomized 63 healthy adults (>64) either to HBOT(n=33) or control arms(n=30) for three months. Primary endpoint included the general cognitive function measured post intervention/control. Cerebral blood flow (CBF) was evaluated by perfusion magnetic resonance imaging.There was a significant group-by-time interaction in global cognitive function post-HBOT compared to control (p=0.0017). The most striking improvements were in attention (net effect size=0.745) and information processing speed (net effect size=0.788).Voxel-based analysis showed significant cerebral blood flow increases in the HBOT group compared to the control group in the right superior medial frontal gyrus (BA10), right and left supplementary motor area (BA6), right middle frontal gyrus (BA6), left middle frontal gyrus (BA9), left superior frontal gyrus (BA8) and the right superior parietal gyrus (BA7).In this study, HBOT was shown to induce cognitive enhancements in healthy aging adults via mechanisms involving regional changes in CBF. The main improvements include attention, information processing speed and executive functions, which normally decline with aging.

Hyperbaric oxygen therapy effects on pulmonary functions: a prospective cohort study.

BACKGROUND: Oxygen toxicity is one potential side effect of hyperbaric oxygen therapy (HBOT). Previous small studies showed mild reductions in pulmonary functions reflecting reductions in small airway conductance after repetitive hyperbaric oxygen sessions. However, there are no updated data with well performed pulmonary tests that address the pulmonary effect of the currently used HBOT protocols. The aim of this study was to evaluate the effect of HBOT on pulmonary functions of patients receiving the currently used HBOT protocol. METHODS: Prospective analysis included patients, 18 years or older, scheduled for 60 daily HBOT sessions between 2016 and 2018. Each session was 90 min of 100% oxygen at 2 ATA with 5 min air breaks every 20 min, 5 days per week. Pulmonary functions, measured at baseline and after HBOT, included forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1) and peak expiratory flow rate (PEF). RESULTS: The mean age was 60.36 ± 15.43 and 62.5% (55/88) were males. Most of the patients (83/88, 94.3%) did not have any pulmonary disease prior to inclusion and 30.7% (27/88) had a history of smoking. Compared to baseline values, at the completion of 60 HBOT sessions, there were no significant changes in FEV1 (0.163), FEV1/FVC ratio (0.953) and FEF25-75% (0.423). There was a statistically significant increase though not clinically relevant increase in FVC (0.1 ± 0.38 l) and PEF (0.5 ± 1.4 l) with a 0.014 and 0.001 respectively. CONCLUSION: Regarding pulmonary functions, repeated hyperbaric oxygen exposure based on the currently used HBOT protocol is safe. Surprisingly, there was a modest non clinically significant though statistically significant improvement in PEF and FVC in the current cohort of patients who were without chronic lung diseases. TRIAL REGISTRATION: Clinicaltrials.gov, trial ID: NCT03754985 , (Nov 2018) Retrospectively registered.

Hyperbaric oxygen can induce angiogenesis and recover erectile function.

Erectile dysfunction (ED) is caused by microvascular or macrovascular insufficiency in the majority of patients. Recent studies have shown that hyperbaric oxygen therapy (HBOT) can induce angiogenesis in different body organs. The effect of HBOT on the non-surgery-related ED has not been investigated yet. The aim of the current study was to evaluate the effects of HBOT on sexual function and penile vascular bed in non-surgical ED patients. A prospective analysis of patients suffering from chronic ED treated with 40 daily HBOT sessions. Clinical efficacy was assessed using the International Index of Erectile Function questionnaire (IIEF) and a global efficacy question (GEQ). The effect on the penile vascular bed was evaluated by perfusion MRI. Thirty men (mean age of 59.2 ± 1.4) suffering from ED for 4.2 ± 0.6 years completed the protocol. HBOT significantly improved all IIEF domains by 15-88% (p < 0.01). Erectile function improved by 88% (p < 0.0001) and 80% of the patients reported positive outcome according to the GEQ. Angiogenesis was indicated by perfusion MRI that showed a significant increase by 153.3 ± 43.2% of K-trans values in the corpous cavernous (p < 0.0001). HBOT can induce penile angiogenesis and improve erectile function in men suffering from EcD. HBOT reverses the basic common pathophysiology, atherosclerosis and decreased penile perfusion, responsible for most cases of ED.

Nonhealing Wounds Caused by Brown Spider Bites: Application of Hyperbaric Oxygen Therapy.

BACKGROUND: Bites by Loxosceles spiders (also known as recluse spiders or brown spiders) can cause necrotic ulcerations of various sizes and dimensions. The current standard of care for brown spider bites includes analgesics, ice, compression, elevation, antihistamines, and surgical debridement. Hyperbaric oxygen therapy (HBOT) in the treatment of brown spider bites has been administered in the early stage of ulceration, or 2 to 6 days after the bite. Unfortunately, the diagnosis of spider bite-related ulcers is often delayed and weeks or months may elapse before HBOT is considered. OBJECTIVE: To evaluate the effect of HBOT on nonhealing wounds caused by brown spider bites in the late, chronic, nonhealing stage. METHODS: Analysis of 3 patients with brown spider-bite healing wounds treated at The Sagol Center for Hyperbaric Medicine and Research in Israel. Patients presented 2 to 3 months after failure of other therapies including topical dressings, antibiotics, and corticosteroids. All patients were treated with daily 2 ATA (atmospheres absolute) with 100% oxygen HBOT sessions. RESULTS: All 3 patients were previously healthy without any chronic disease. Their ages were 30, 42, and 73 years. They were treated once daily for 13, 17, and 31 sessions, respectively. The wounds of all 3 patients healed, and there was no need for additional surgical intervention. There were no significant adverse events in any of the patients. CONCLUSIONS: Microvascular injury related to brown spider bites may culminate in ischemic nonhealing wounds even in a relatively young, healthy population. Hyperbaric oxygen therapy should be considered as a valuable therapeutic tool even months after the bite.