Hyperbaric Oxygen Therapy Counters Oxidative Stress/Inflammation-Driven Symptoms in Long COVID-19 Patients: Preliminary Outcomes.

Long COVID-19 patients show systemic inflammation and persistent symptoms such as fatigue and malaise, profoundly affecting their quality of life. Since improving oxygenation can oppose inflammation at multiple tissue levels, we hypothesized that hyperbaric oxygen therapy (HBOT) could arrest inflammation progression and thus relieve symptoms of COVID-19. We evaluated oxy-inflammation biomarkers in long COVID-19 subjects treated with HBOT and monitored with non-invasive methods. Five subjects (two athletes and three patients with other comorbidities) were assigned to receive HBOT: 100% inspired O2 at 2.4 ATA in a multiplace hyperbaric chamber for 90 min (three athletes: 15 HBOT × 5 days/wk for 3 weeks; two patients affected by Idiopathic Sudden Sensorineural Hearing Loss: 30 HBOT × 5 days/wk for 6 weeks; and one patient with osteomyelitis: 30 HBOT × 5 days/wk for week for 6 weeks and, after a 30-day break, followed by a second cycle of 20 HBOT). Using saliva and/or urine samples, reactive oxygen species (ROS), antioxidant capacity, cytokines, lipids peroxidation, DNA damage, and renal status were assessed at T1_pre (basal level) and at T2_pre (basal level after treatment), and the results showed attenuated ROS production, lipid peroxidation, DNA damage, NO metabolites, and inflammation biomarker levels, especially in the athletes post-treatment. Thus, HBOT may represent an alternative non-invasive method for treating long COVID-19-induced long-lasting manifestations of oxy-inflammation.

Relative hypoxemia at depth during breath-hold diving investigated through arterial blood gas analysis and lung ultrasound.

Pulmonary gas exchange in breath-hold diving (BHD) consists of a progressive increase in arterial partial pressures of oxygen ([Formula: see text]) and carbon dioxide ([Formula: see text]) during descent. However, recent findings have demonstrated that [Formula: see text] does not consistently rise in all subjects. This study aimed at verifying and explaining [Formula: see text] derangements during BHD analyzing arterial blood gases and searching for pulmonary alterations with lung ultrasound. After ethical approval, 14 fit breath-hold divers were included. Experiments were performed in warm water (temperature: 31°C). We analyzed arterial blood gases immediately before, at depth, and immediately after a breath-hold dive to -15 m of fresh water (mfw) and -42 mfw. Signs of lung interstitial edema and atelectasis were searched simultaneously with a marinized lung ultrasound. In five subjects (-15 mfw) and four subjects (-42 mfw), the [Formula: see text] at depth seems to decrease instead of increasing. [Formula: see text] and lactate showed slight variations. At depth, no lung ultrasound alterations were seen except in one subject (hypoxemia and B-lines at -15 mfw; B-lines at the surface). Lung interstitial edema was detected in 3 and 12 subjects after resurfacing from -15 to -42 mfw, respectively. Two subjects developed hypoxemia at depth and a small lung atelectasis (a focal pleural irregularity of triangular shape, surrounded by thickened B-lines) after resurfacing from -42 mfw. Current experiments confirmed that some BH divers can experience hypoxemia at depth. The hypothesized explanation for such a discrepancy is lung atelectasis, which could not be detected in all subjects probably due to limited time available at depth.NEW & NOTEWORTHY During breath-hold diving, arterial partial pressure of oxygen ([Formula: see text]) and arterial partial pressure of carbon dioxide ([Formula: see text]) are believed to increase progressively during descent, as explained by theory, previous end-tidal alveolar gas measurements, and arterial blood gas analysis in hyperbaric chambers. Recent experiments in real underwater environment found a paradoxical [Formula: see text] drop at depth in some divers. This work confirms that some breath-hold divers can experience hypoxemia at depth. The hypothesized explanation for such a discrepancy is lung atelectasis, as suggested by lung ultrasound findings.

Comparison between Arterial Blood Gases and Oxygen Reserve Index™ in a SCUBA Diver: A Case Report.

Hypoxia and hyperoxia are both worrisome issues potentially affecting SCUBA divers, but validated methods to monitor these two conditions underwater are still lacking. In this experiment, a volunteer SCUBA diver was equipped with a pulse oximeter to detect peripheral oxygen saturation (SpO2) and a device to monitor the oxygen reserve index (ORi™). ORi™ values were compared with arterial blood oxygen saturation (SaO2) and the partial pressure of oxygen (PaO2) obtained from the cannulated right radial artery at three steps: at rest out of water; at -15 m underwater after pedaling on a submerged bike; after resurfacing. SpO2 and ORi™ mirrored the changes in SaO2 and PaO2, confirming the expected hyperoxia at depth. To confirm the potential usefulness of an integrated SpO2 and ORi™ device, further studies are needed on a broader sample with different underwater conditions and diving techniques.

Dopamine/BDNF loss underscores narcosis cognitive impairment in divers: a proof of concept in a dry condition.

PURPOSE: Divers can experience cognitive impairment due to inert gas narcosis (IGN) at depth. Brain-derived neurotrophic factor (BDNF) rules neuronal connectivity/metabolism to maintain cognitive function and protect tissues against oxidative stress (OxS). Dopamine and glutamate enhance BDNF bioavailability. Thus, we hypothesized that lower circulating BDNF levels (via lessened dopamine and/or glutamate release) underpin IGN in divers, while testing if BDNF loss is associated with increased OxS. METHODS: To mimic IGN, we administered a deep narcosis test via a dry dive test (DDT) at 48 msw in a multiplace hyperbaric chamber to six well-trained divers. We collected: (1) saliva samples before DDT (T0), 25 msw (descending, T1), 48 msw (depth, T2), 25 msw (ascending, T3), 10 min after decompression (T4) to dopamine and/or reactive oxygen species (ROS) levels; (2) blood and urine samples at T0 and T4 for OxS too. We administered cognitive tests at T0, T2, and re-evaluated the divers at T4. RESULTS: At 48 msw, all subjects experienced IGN, as revealed by the cognitive test failure. Dopamine and total antioxidant capacity (TAC) reached a nadir at T2 when ROS emission was maximal. At decompression (T4), a marked drop of BDNF/glutamate content was evidenced, coinciding with a persisting decline in dopamine and cognitive capacity. CONCLUSIONS: Divers encounter IGN at - 48 msw, exhibiting a marked loss in circulating dopamine levels, likely accounting for BDNF-dependent impairment of mental capacity and heightened OxS. The decline in dopamine and BDNF appears to persist at decompression; thus, boosting dopamine/BDNF signaling via pharmacological or other intervention types might attenuate IGN in deep dives.

Emergency Medicine Cases in Underwater and Hyperbaric Environments: The Use of in situ Simulation as a Learning Technique.

INTRODUCTION: Hyperbaric chambers and underwater environments are challenging and at risk of serious accidents. Personnel aiming to assist patients and subjects should be appropriately trained, and several courses have been established all over the world. In healthcare, simulation is an effective learning technique. However, there have been few peer-reviewed articles published in the medical literature describing its use in diving and hyperbaric medicine. METHODS: We implemented the curriculum of the Master's degree in hyperbaric and diving medicine held at the University of Padova with emergency medicine seminars created by the faculty and validated by external experts. These seminars integrated traditional lectures and eight in situ simulation scenarios. RESULTS: For the hyperbaric medicine seminar, simulations were carried out inside a real hyperbaric chamber at the ATIP Hyperbaric Treatment Centre, only using air and reproducing compression noise without pressurization to avoid damages to the manikins. The four scenarios consisted of hyperoxic seizures, pneumothorax, hypoglycemia, and sudden cardiac arrest. Furthermore, we added a hands-on session to instruct participants to prepare an intubated patient undergoing hyperbaric oxygen treatment with a checklist and simulating the patient transfer inside and outside the hyperbaric chamber. The diving medicine seminar was held at the Y-40 The Deep Joy pool in Montegrotto Terme (Italy), also involving SCUBA/breath-hold diving (BHD) instructors to rescue subjects from the water. These diving medicine scenarios consisted of neurologic syndrome ("taravana/samba") in BHD, drowning of a breath-hold diver, pulmonary barotrauma in BHD, and decompression illness in a SCUBA diver. CONCLUSION: With this experience, we report the integration of simulation in the curriculum of a teaching course in diving and hyperbaric medicine. Future studies should be performed to investigate learning advantages, concept retention, and satisfaction of participants.

The Role of Hyperbaric Oxygen Treatment for COVID-19: A Review.

The recent coronavirus disease 2019 (COVID-19) pandemic produced high and excessive demands for hospitalizations and equipment with depletion of critical care resources. The results of these extreme therapeutic efforts have been sobering. Further, we are months away from a robust vaccination effort, and current therapies provide limited clinical relief. Therefore, several empirical oxygenation support initiatives have been initiated with intermittent hyperbaric oxygen (HBO) therapy to overcome the unrelenting and progressive hypoxemia during maximum ventilator support in intubated patients, despite high FiO2. Overall, few patients have been successfully treated in different locations across the globe. More recently, less severe patients at the edge of impending hypoxemia were exposed to HBO preventing intubation and obtaining the rapid resolution of symptoms. The few case descriptions indicate large variability in protocols and exposure frequency. This summary illustrates the biological mechanisms of action of increased O2 pressure, hoping to clarify more appropriate protocols and more useful application of HBO in COVID-19 treatment.

Arterial blood gases in divers at surface after prolonged breath-hold.

PURPOSE: Adaptations during voluntary breath-hold diving have been increasingly investigated since these athletes are exposed to critical hypoxia during the ascent. However, only a limited amount of literature explored the pathophysiological mechanisms underlying this phenomenon. This is the first study to measure arterial blood gases immediately before the end of a breath-hold in real conditions. METHODS: Six well-trained breath-hold divers were enrolled for the experiment held at the "Y-40 THE DEEP JOY" pool (Montegrotto Terme, Padova, Italy). Before the experiment, an arterial cannula was inserted in the radial artery of the non-dominant limb. All divers performed: a breath-hold while moving at the surface using a sea-bob; a sled-assisted breath-hold dive to 42 m; and a breath-hold dive to 42 m with fins. Arterial blood samples were obtained in four conditions: one at rest before submersion and one at the end of each breath-hold. RESULTS: No diving-related complications were observed. The arterial partial pressure of oxygen (96.2 ± 7.0 mmHg at rest, mean ± SD) decreased, particularly after the sled-assisted dive (39.8 ± 8.7 mmHg), and especially after the dive with fins (31.6 ± 17.0 mmHg). The arterial partial pressure of CO2 varied somewhat but after each study was close to normal (38.2 ± 3.0 mmHg at rest; 31.4 ± 3.7 mmHg after the sled-assisted dive; 36.1 ± 5.3 after the dive with fins). CONCLUSION: We confirmed that the arterial partial pressure of oxygen reaches hazardously low values at the end of breath-hold, especially after the dive performed with voluntary effort. Critical hypoxia can occur in breath-hold divers even without symptoms.

Clinical and morphological effects of hyperbaric oxygen therapy in patients with interstitial cystitis associated with fibromyalgia.

BACKGROUND: Interstitial Cystitis (IC) is a debilitating disorder of the bladder, with a multifactorial and poorly understood origin dealing with microcirculation repeated damages. Also Fibromyalgia (FM) is a persistent disorder whose etiology is not completely explained, and its theorized alteration of pain processing can compromise the quality of life. Both these conditions have a high incidence of conventional therapeutic failure, but recent literature suggests a significant beneficial response to Hyperbaric Oxygen Therapy (HBOT). With this study, this study we evaluated the effects of HBOT on quality of life, symptoms, urodynamic parameters, and cystoscopic examination of patients suffering from both IC and FM. METHODS: We structured an observational clinical trial design with repeated measures (questionnaires, urodynamic test, and cystoscopy) conducted before and 6 months after a therapeutic protocol with hyperbaric oxygen for the treatment of patients suffering from both IC and FM. Patients were exposed to breathing 100% oxygen at 2 atm absolute (ATA) in a multiplace pressure chamber for 90 min using an oro-nasal mask. Patients undertook a cycle of 20 sessions for 5 days per week, and a second cycle of 20 sessions after 1 week of suspension. RESULTS: Twelve patients completed the protocol. Changes after HBOT were not significant, except for hydrodistension tolerance (mean pre-treatment: 409.2 ml; mean post-treatment: 489.2 ml; p < 0.05). A regression of petechiae and Hunner's ulcers was also noted 6 months after the completion of HBOT. CONCLUSIONS: Our study showed no improvement of symptoms, quality of life, and urodynamic parameters, except for hydrodistension, and a slight improvement in cystoscopic pattern. However, to date, we could not demonstrate the significance of overall results to justify the use of HBOT alone in patients with IC and FM. This observation suggests that additional studies are needed to better understand if HBOT could treat this subset of patients. TRIAL REGISTRATION: NCT03693001 ; October 2, 2018. Retrospectively registered.

Osteonecrosis in Children and Adolescents With Acute Lymphoblastic Leukemia: Early Diagnosis and New Treatment Strategies.

BACKGROUND/AIM: In the last few decades, treatment strategies for acute lymphoblastic leukemia (ALL) have been associated not only with improvement of prognosis, but also with an increasing rate of late complication as osteonecrosis (ON). Herein, the cumulative incidence, risk factors, new conservative therapeutic strategies as hyperbaric oxygen therapy (HBO), and outcome of symptomatic ON were studied in pediatric patients with ALL. PATIENTS AND METHODS: Between 2000 and 2017, 495 children and young adolescents with a diagnosis of ALL were evaluated. All the symptomatic patients underwent magnetic resonance imaging (MRI) to detect bone vascularization and structure. RESULTS: Twenty-three out of 495 patients presented ON (4.6%). ON was associated with an older age (p<0.0001) and a higher steroid dose (p=0.0013). All the patients underwent standard therapies and HBO was performed in 8 of 23 patients. During the follow-up, 15 patients were stable: 6 were totally asymptomatic, 5 complained of pain during activity, and 4 presented mild function limitation. CONCLUSION: Our data highlight the importance of early diagnosis of ON by screening MRI in asymptomatic patients, in order to start conservative treatment strategies. Moreover, HBO could have beneficial effects on ON patients.

Arterial Blood Gas Analysis in Breath-Hold Divers at Depth.

The present study aimed to evaluate the partial pressure of arterial blood gases in breath-hold divers performing a submersion at 40 m. Eight breath-hold divers were enrolled for the trials held at "Y-40 THE DEEP JOY" pool (Montegrotto Terme, Padova, Italy). Prior to submersion, an arterial cannula in the radial artery of the non-dominant limb was positioned. All divers performed a sled-assisted breath-hold dive to 40 m. Three blood samplings occurred: at 10 min prior to submersion, at 40 m depth, and within 2 min after diver's surfacing and after resuming normal ventilation. Blood samples were analyzed immediately on site. Six subjects completed the experiment, without diving-related problems. The theoretically predicted hyperoxia at the bottom was observed in 4 divers out of 6, while the other 2 experienced a reduction in the partial pressure of oxygen (paO2) at the bottom. There were no significant increases in arterial partial pressure of carbon dioxide (paCO2) at the end of descent in 4 of 6 divers, while in 2 divers paCO2 decreased. Arterial mean pH and mean bicarbonate ( HCO 3 - ) levels exhibited minor changes. There was a statistically significant increase in mean arterial lactate level after the exercise. Ours was the first attempt to verify real changes in blood gases at a depth of 40 m during a breath-hold descent in free-divers. We demonstrated that, at depth, relative hypoxemia can occur, presumably caused by lung compression. Also, hypercapnia exists at depth, to a lesser degree than would be expected from calculations, presumably because of pre-dive hyperventilation and carbon dioxide distribution in blood and tissues.

Safety of transport and hyperbaric oxygen treatment in critically-ill patients from Padua hospitals into a centrally-located, stand-alone hyperbaric facility.

INTRODUCTION: Some patients admitted to the intensive care unit (ICU) might require repetitive hyperbaric oxygen treatment (HBOT) while receiving critical care. In such cases, the presence of a hyperbaric chamber located inside or near an ICU is preferable; however, this set-up is not always possible. In Padua, the "Associazione Tecnici IPerbarici" hyperbaric centre is a stand-alone facility outside of a hospital. Despite this, selected ICU patients receive HBOT at this facility. METHODS: We retrospectively reviewed the medical records from 2003 to 2013 of 75 consecutive, critically-ill patients, 28 of whom were initially intubated and mechanically ventilated whilst undergoing HBOT. We evaluated the methods adopted in Padua to guarantee the safety and continuity of care during transfer for and during HBOT in this specially-equipped multiplace chamber. RESULTS: The 75 patients collectively received 315 HBOT sessions, 192 of which were with the patients intubated and mechanically ventilated. The diagnoses ranged from necrotizing fasciitis to post-surgical sepsis and intracranial abscess. We obtained full recovery for 73 patients. Two deaths were recorded not in close time relation to HBOT. CONCLUSIONS: With meticulous monitoring, efficient transport and well-trained personnel, the risks associated with transportation and HBOT can be acceptable for the referring physician.

Effect of hyperbaric oxygenation and gemcitabine on apoptosis of pancreatic ductal tumor cells in vitro.

BACKGROUND: Gemcitabine is first-line therapy for advanced pancreatic ductal adenocarcinoma (PDAC) with a poor survival and response rate. Hyperbaric oxygenation (HBO) enhances delivery of oxygen to hypoxic tumor cells and increases their susceptibility to cytotoxic effects of chemotherapy. We hypothesized that the anticancer activity of gemcitabine (GEM) may be enhanced if tumor cells are placed in an oxygen-rich environment. The present study evaluated the effects of gemcitabine, HBO and their combination on apoptosis of tumor cells. MATERIALS AND METHODS: PANC-1 and AsPc-1 PDAC tumor cell lines were used. Cultured tumor cells were treated with GEM at its growth-inhibitory concentration (IC50) and HBO at 2.5 ATA for 90 min or a combination of both (HBO then GEM and GEM then HBO). Twenty-four hours later, apoptotic cells in each group were analyzed and the apoptotic index (AI) was calculated. RESULTS: PANC-1 cell line: HBO alone had no effect on AI: 6.5 ± 0.1 vs. 5.9 ± 0.1. HBO before and after gemcitabine did not further increase AI: 8.2 ± 0.1 (HBO-GEM), 8.5 ± 0.1 (GEM-HBO) vs. 8.1 ± 0.1 (GEM). The combination of HBO and gemcitabine significantly increased AI: 10.7 ± 0.02 (p<0.001 vs. all groups). AsPc-1 cell line: HBO-alone had no effect on AI: 5.9 ± 0.1 vs. 5.9 ± 0.1. HBO before and after gemcitabine did not further increase AI: 8.2 ± 0.1 (HBO-GEM), 8.4 ± 0.1 (GEM-HBO) vs. 8.0 ± 0.1 (GEM). The combination of HBO and gemcitabine significantly increased AI: 9.7 ± 0.1 (p<0.001 vs. all groups). CONCLUSION: HBO-alone, whether administered before and after gemcitabine has no effect on apoptosis of PDAC cells in vitro. HBO significantly enhanced gemcitabine-induced apoptosis when administered during gemcitabine. Our findings suggest that the time window would be critical for using HBO as adjuvant to chemotherapy.

The effect of acute exposure to hyperbaric oxygen on respiratory system mechanics in the rat.

PURPOSE: This study was designed to investigate the possible effects of acute hyperbaric hyperoxia on respiratory mechanics of anaesthetised, positive-pressure ventilated rats. METHODS: We measured respiratory mechanics by the end-inflation occlusion method in nine rats previously acutely exposed to hyperbaric hyperoxia in a standard fashion. The method allows the measurements of respiratory system elastance and of both the "ohmic" and of the viscoelastic components of airway resistance, which respectively depend on the newtonian pressure dissipation due to the ohmic airway resistance to air flow, and on the viscoelastic pressure dissipation caused by respiratory system tissues stress-relaxation. The activities of inducible and endothelial NO-synthase in the lung's tissues (iNOS and eNOS respectively) also were investigated. Data were compared with those obtained in control animals. RESULTS: We found that the exposure to hyperbaric hyperoxia increased respiratory system elastance and both the "ohmic" and viscoelastic components of inspiratory resistances. These changes were accompanied by increased iNOS but not eNOS activities. CONCLUSIONS: Hyperbaric hyperoxia was shown to acutely induce detrimental effects on respiratory mechanics. A possible causative role was suggested for increased nitrogen reactive species production because of increased iNOS activity.

Hyperbaric oxygen treatment of superficial soft tissue lesions in children with oncologic disease.

This study aimed to assess the feasibility and results of hyperbaric oxygen therapy (HOT) as supportive treatment of lesions of superficial soft tissues in children with oncological diseases. This was a retrospective analysis and review of all records of children observed at the Pediatric Hematology-Oncology Department of the University of Padova and treated adjuvantly with HOT. Between 1996 and 2010, 12 patients (5 males and 7 females, median age 7 years, range 0.5-16) underwent HOT. The effectiveness of HOT varied according to the lesion treated. Ten out of 12 patients were cured. Efficacy was most questionable in 2 patients with skin graft and flaps at risk. Compliance to therapy was close to 100%. In just one case, HOT was interrupted for the appearance of local skin metastases close to the site of primary tumor. HOT showed itself to be safe and effective in most patients even those immunocompromised or critically ill.