"Comparative Analysis: Effects of Mild and High-Pressure Hyperbaric Oxygen Therapy (HBOT) on Cytokine Modulation both Immune and Inflammatory Pathways"

Is oxygen an antibiotic?

HIGH oxygen content within the plasma that can supplement, or even supplant, the hemoglobin-bound oxygen can be achieved by use of hyperbaric oxygen administration. In 1960, Boerema et al. 1 exsanguinated pigs and then reanimated them by treatment in a hyperbaric chamber, Forty years later, hyperbaric therapy can be life saving when used as temporizing or definitive therapy in cases of severe anemia when transfusion is difficult to achieve or refused.

Terapi Oksigen Hiperbarik (HBOT) semakin sering digunakan di berbagai bidang medis, perawatan, dan praktik kesehatan. Menjadi intervensi penting dengan mekanisme tindakan yang tidak dipahami dengan baik. Terapi Oksigen Hiperbarik adalah salah satu metode pengobatan yang dilakukan dengan menyediakan 100% oksigen murni yang dihirup oleh pasien di ruangan khusus dengan udara bertekanan tinggi. Tekanan udara yang meningkat pada ruang Hiperbarik menyebabkan paru pasien menyerap lebih banyak oksigen daripada biasanya, yang dapat membantu menyembuhkan berbagai penyakit. Diharapkan adanya kajian ilmiah, ulasan dan diskusi tentang terapi heperbaric dan pencarian literatur tentang penggunaannya dapat bermanfaat bagi tim medis baik perawat, dokter, pekerja kesehatan lainnya dan masyarakat, sehingga mereka dapat meningkatkan pengetahuan, berdasarkan fisiologi, patologi, fisika, farmakologi, manfaat, indikasi dan perawatan tentang terapi hiperbarik sehingga dapat diterapkan dalam berbagai bidang yang diperlukan.

Introduction: Patients with liver disease generally have a serious clinical condition that can rapidly worsen, making the wait until liver transplantation or post-surgery a poor prognosis. Hyperbaric oxygen therapy has therefore been described in some studies as an alternative in these cases, as it mitigates the effects of the diseases and liver transplantation. Objective: To describe the effects of hyperbaric oxygen therapy in the pre- and post-operative periods of patients undergoing liver transplantation. Methods: This is an Integrative Review using the PubMed and Web Of Science databases. The following descriptors were used: “Hyperbaric oxygenation”, “Liver transplantation” and “Hyperbaric oxygen therapy” with the Boolean operator “AND”, and articles of relevance to the topic were selected. Initially, 49 articles were selected, all published in the last 20 years, in Portuguese and/or English. After analysis, 6 articles matched the proposed objective. Results: It can be seen that intraoperative systemic O2 content affects postoperative recovery in patients undergoing liver transplantation. Early hyperbaric oxygen therapy acts as a protector in reducing the severity of hepatocyte ischemia/reperfusion injury. Hyperbaric oxygen therapy also influences the immune response of patients undergoing liver transplantation, reducing incompatibility. Still on the subject of the immunomodulatory effects of hyperbaric oxygen therapy, this therapy has been shown to be effective in helping to prevent post-operative infections by improving the antibacterial activity of immune cells and increasing the bactericidal effect of antibiotics. In the case of patients on the waiting list for liver transplants, a reduction in the number and intensity of encephalopathy episodes, an improvement in pruritus and a feeling of well-being were observed after treatment with oxygen therapy. In terms of early allograft dysfunction, it was shown that patients with dysfunction had lower O2 values in the anepathic and neo-hepatic phases when compared to patients without dysfunction in the post-operative period. In addition, during the anepathic phase, the content of the SatO2 level was also lower in the group with dysfunction than in those without. Conclusion: Hyperbaric oxygen therapy is beneficial in liver preservation, as it helps to maintain liver function, prolong liver preservation time and improve the outcome of liver transplantation.

Hyperbaric oxygen therapy (HBOT) is US FDA approved for a short list of 14 severe, life-threatening conditions. These FDA approved conditions range from osteomyelitis, osteonecrosis and gangrene to non-healing wounds, diabetic neuropathy, crush injuries, radiation burns and more. When applied in acute and severe conditions, this therapy is noninvasive, safe, and effective in promoting patient recovery, improved healing times, and increased tissue regeneration. Alternatively, chronic inflammatory illnesses affect a larger population, cost our medical system billions of dollars every year, impair our quality of life, and reduce our ability to contribute to society. Some of these conditions include autoimmunity, neurodegenerative and musculoskeletal degenerative diseases, cardiovascular disease, cancer and many others. Common denominators for many of these illnesses include chronic inflammation, metabolic and mitochondrial dysfunction and immune dysregulation. The majority of studies for HBOT point to about 10 very specific mechanisms of action when used for the more conventionally treated conditions. There is mounting evidence that the mechanisms of action for these “on label” acute and severe cases are similar or even identical to those required for treating other chronic illnesses to improve their outcomes and recovery times. Hyperbaric oxygen can be delivered a number of ways, from mild pressure to high pressure and from 21% oxygen through 100% oxygen. Current research also shows that intermittent and relative hyperoxia-hypoxia is a strong stimulator of many cell signaling and epigenetic signaling cascades used for the promotion of and adaptation to improved cellular healing and regenerative responses. The research on these concepts is currently in its infancy but recent studies have shown that HBOT, through its influences on hypoxia-inducible factor 1α, reactive oxygen species signaling and sirtuin stimulation can help to promote hormonal balance, nervous system balance, improve mitochondrial performance, reduce inflammation and stimulate cell and tissue repair and regeneration for many different health concerns. Another study published in 2019 also showed us that using hyperbaric oxygen can also stimulate telomere growth and reduce cellular senescence, putting HBOT within the category of optimal modalities to be considered for a well-rounded antiaging and regenerative medicine approach to improved health and quality of life.

Hyperbaric oxygen therapy (HBO) is increasingly used in a number of areas of medical practice. It is a unique intervention whose method of action is not well understood. Clinicians may request its use for their patients, but often will not fully understand its mechanisms. It is hoped that this review and discussion of HBO and the literature surrounding its use may be useful to clinicians who are unsure whether their patients will benefit from this exciting intervention. Hyperbaric oxygen therapy is defined by the Undersea and Hyperbaric Medical Society (UHMS) as a treatment in which a patient intermittently breathes 100% oxygen while the treatment chamber is pressurized to a pressure greater than sea level (1 atmosphere absolute, ATA).1 The pressure increase must be systemic, and may be applied in monoplace (single person) or multiplace chambers. Multiplace chambers are pressurized with air, with oxygen given via face-mask, hood tent or endotracheal tube; while monoplace chambers are pressurized with oxygen. We began by obtaining the most recent UHMS committee report,1 and performed Medline searches (1966 to present), with the search terms ‘hyperbaric’ and ‘oxygen’, combining this basic search with searches for each of the thirteen indications recommended by the UHMS. Using information from these papers, and the resulting references, this paper outlines the history, physiology, current indications for and effects of hyperbaric oxygen therapy. Hyperbaric therapy was first documented in 1662, when Henshaw built the first hyperbaric chamber, or ‘domicilium’.2 Since this time, reports of beneficial effects from increased pressure have increased, and by 1877, chambers were used widely for many conditions, though there was little scientific rationale or evidence. In 1879, the surgical application of hyperbaric therapy in prolonging safe anaesthesia was realized and explored.3 In 1927, Cunningham4 reported improvement in circulatory disorders at sea level … Address correspondence to Dr C.N.A. Bell, Division of Oral & Maxillo-Facial Surgery, Bristol Dental Hospital, Lower Maudlin Street, Bristol BS1 2LY. e-mail: chris.bell{at}bristol.ac.uk

INTRODUCTION: Hyperbaric oxygen therapy (HBOT) indeed holds significant therapeutic potential across various medical conditions, primarily by increasing the concentration of oxygen delivered to tissues under pressure. Saturating tissues with oxygen allows for the effective alleviation of underlying hypoxia, facilitating healing, tissue repair and mechanisms of action leads to reducing concentration of pro-inflammatory acute phase proteins, interleukins, and cytokines. Conversely, HBOT while also boosting levels of growth factors and other cytokines that promote angiogenesis. REVIEW METHODS: The article was complied by analyzing data from PubMed and Google Scholar regarding effects of hyperbaric therapy. THE STATE OF KNOWLEDGE: Studies indicate that HBOT provides numerous opportunities in the treatment of extensive diseases acress various systems. Neurodegenerative disorders involve progressive nerve cell damage leading to motor or cognitive decline, exacerbated by oxidative stress and inflammation. HBOT has shown promise in delaying disease onset by improving mitochondrial dysfunction in motor neuron disease. In case of intestinal obstruction HBOT reduces intestinal gas volume, diameter of obstructed loops, and improves intestinal contractility. Significant benefits have been observed in conditions such as Crohn's disease and ulcerative colitis. Hyperbaric therapy presents potential benefits for the infertility, improving the environment for blastocyst implantation and pregnancy. CONCLUSION: There is no doubt that HBOT has a beneficial impact on treatment of many systems such as the nervous, cardiovascular, digestive, and skeletal. This innovative approach of hyperbaric therapy extends to selected disorders such as neurodegenerative diseases, Crohn's disease, ulcerative colitis, and infertility.

Review the mechanisms of action and clinical application of hyperbaric oxygen therapy (HBOT) based on human and veterinary clinical and experimental literature. Pubmed and Veterinary Information Network databases were searched for human and veterinary journal articles on hyperbaric therapy in clinically applicable situations. Historical reference searches on several articles in addition to basic physiologic concepts were also reviewed. HBOT has gained acceptance as an adjunctive treatment in clinical conditions other than diving-related injuries, such as select problem wounds and central nervous system diseases, in human medicine. Access to hyperbaric therapy has increased and ongoing research has furthered understanding of the mechanisms and potential therapeutic uses of HBOT. Several animal models have been utilized to examine the effects of HBOT; primarily rodents (mice, rats) and rabbits but also dogs, cats, and pigs. Data related to animal model research as it pertains to clinical application of HBOT is reviewed. There is a substantial body of literature that has examined the adverse and beneficial effects of HBOT in animal models. As technology becomes more readily available to clinical practice and more clinical trials are performed to define its effectiveness, HBOT may be considered as an additional therapeutic option in many conditions including select problem wounds, spinal cord injury, and cerebral ischemic injury. Understanding the mechanisms by which HBOT exerts its effects will help guide research and use of the modality in clinical patients.

Background: Hyperbaric oxygen therapy (HBOT) is a therapeutic modality in which pure and pressurized oxygen is delivered to the patient, causing tissue hyperoxygenation and consequent improvements in the inflammatory state, immune defense capacity, and healing. It is performed in pressurized chambers with oxygen, specific for the therapy. Dioctophyme renale, a nematode, is a parasite in mammals that causes severe, chronic, and progressive kidney damage. It is usually diagnosed through abdominal ultrasonography. Most cases are asymptomatic, and the treatment of choice is surgery. This report concerns 2 cases of conditioning with HBOT before laparoscopic right nephrectomy.Cases: Two adult bitches, both of mixed breed, parasitized naturally by Dioctophyme renale in the right kidney, and weretreated at the Veterinary Hospital. The bitch in case 1 had no clinical signs of the disease, whereas the bitch in case 2 hadhematuria for 3 years. Parasite eggs were not found in the urine of either dog. Both dogs underwent 2 presurgical HBOTsessions, 24 h apart, at a pressure of 2 absolute total atmospheres for 30 min. Immediately after the 2nd session, generalanesthesia was induced, and the dogs underwent laparoscopic right nephrectomy in the left lateral decubitus position,and surgical access was through 3 portals in the right flank. Hemostasis was achieved with titanium clips in case 1 andwith bipolar forceps with impedance control in case 2. The parasitized kidneys were placed in a tissue extractor bag andremoved from de cavity, and the surgical wound was sutured in 3 layers. Three male parasites were removed from thekidney in case 1 and one male parasite from that in case 2. Neither patient had free parasites in the abdominal cavity. Nointraoperative or postoperative complications occurred. Hematological examinations revealed improvement in the redblood cell count and a decrease in the serum fibrinogen level in case 1 and a decrease in the red series and an increase inthe serum fibrinogen level in case 2. Both patients had decreased total numbers of leukocytes and platelets.Discussion: Studdies have shown that presurgical hyperbaric conditioning improves renal and hepatic response to ischemia-reperfusion disorders, such as those that may occur during laparoscopies. Such disorders result from the creation of a pneumoperitoneum during the procedure, which increases intra-abdominal pressure. These tissues may receive cytoprotection mediated by the expression of heme-oxygenase 1, an anti-inflammatory substance induced by HBOT. Although the red series was reduced in case 2, it remained within the harmless reference range for the species. The increase in the red series in case 1 demonstrates the potential benefit of HBOT, inasmuch as many animals with D. renale have anemia. Because dioctophymosis leads to chronic kidney damage, a mild inflammatory response is expected. Thus, therapies that reduce systemic inflammation, such as HBOT, are beneficial to patients. Preoperative oxygenation is also recommended in animals undergoing long procedures. The results obtained in these 2 cases were different, but the benefits already proven by the consulted literature indicate that hyperbaric therapy can be advantageous in animals undergoing surgery. HBOT proved to be beneficial in the preoperative conditioning of 2 bitches with Dioctophyme renale, and both animals tolerated very well the therapy. Keywords: hyperbaric oxygen therapy, dioctophymosis, parasitology, giant kidney worm.

Hyperbaric oxygen therapy (HBOT) is discussed as an adjuvant option to treat necrotizing soft tissue infections (NSTI). While the Federal Joint Committee decided in 2007 not to support HBOT for the indication necrotizing fasciitis and Fournier's gangrene, it was decided to accept HBOT for treatment of clostridial myonecrosis for the German health insurance. Thus, in Germany necrotizing fasciitis (NF) is not a confirmed indication for HBOT. Against this background the cons of the clinical benefits of HBOT should be formulated. A literature search (MEDLINE/EMBASE/COCHRANE/manual search) using the keywords "necrotizing fasciitis", "Fournier's gangrene", "necrotizing cellulitis", "necrotizing soft tissue infections" as well as "hyperbaric medicine", "hyperbaric therapy" and "hyperbaric treatment" was carried out. An analysis of the spatial distribution of German hyperbaric oxygen chambers enabling intensive care (HOC-IC) was made. A total of 250 articles with n=2,556 NSTI patients (n=993 treated by HBOT) was found and 50% of the articles were case reports or series. There were only ten retrospective studies comparing the effects of HBOT with non-HBO treatment and none of them verified the benefit of HBOT in NF patients. In Germany only nine hyperbaric oxygen chambers (HOC-IC) enable intensive care. Currently, patient data are not included in scientific studies or multicenter studies, while studies assessing the benefit with higher evidence levels have been required for more than 15 years. The previously published human clinical studies do not confirm any therapeutic benefit of HBOT in NF patients. Any time delay in the start of surgical therapy by HBOT would not be acceptable. In Germany a comprehensive clinical care with HOC is not possible. On average the additional costs of HBO treatment for NF patients is approximately 8,000-25,000<euro>/patient which is not generally reimbursed by health insurance companies. Initializing a register study to assess the benefit of HBOT in NF patients appears feasible and is urgently needed.

BackgroundCardiopulmonary resuscitation (CPR) during hyperbaric oxygen therapy (HBOT) presents unique challenges due to limited access to patients in cardiac arrest (CA) and the distinct physiological conditions present during hyperbaric therapy. Despite these challenges, guidelines specifically addressing CPR during HBOT are lacking. This review aims to consolidate the available evidence and offer recommendations for clinical practice in this context.Materials and methodsA comprehensive literature search was conducted in PubMed, EMBASE, Cochrane Library, and CINAHL using the search string: “(pressure chamber OR decompression OR hyperbaric) AND (cardiac arrest OR cardiopulmonary resuscitation OR advanced life support OR ALS OR life support OR chest compression OR ventricular fibrillation OR heart arrest OR heart massage OR resuscitation)”. Additionally, relevant publications and book chapters not identified through this search were included.ResultsThe search yielded 10,223 publications, with 41 deemed relevant to the topic. Among these, 18 articles (primarily case reports) described CPR or defibrillation in 22 patients undergoing HBOT. The remaining 23 articles provided information or recommendations pertaining to CPR during HBOT. Given the unique physiological factors during HBOT, the limitations of current resuscitation guidelines are discussed.ConclusionsCPR in the context of HBOT is a rare, yet critical event requiring special considerations. Existing guidelines should be adapted to address these unique circumstances and integrated into regular training for HBOT practitioners. This review serves as a valuable contribution to the literature on “CPR under special circumstances”.

It is well known that hyperbaric oxygen (HBO) therapy achieves neuroprotective effects by modulating neuroinflammatory responses. However, its underlying therapeutic mechanisms are not yet fully elucidated. Based on our previous studies, we further investigated whether HBO therapy exerts neuroprotective effects in vivo by regulating the nuclear factor-kappa B (NF-κB)/ mitogen-activated protein kinases (MAPKs) chemokine (C-X-C motif) ligand (CXCL)1 inflammatory pathway. In our study, a rat model of traumatic brain injury (TBI) was established by controlled cortical impact (CCI) to verify that the expression of CXCL1 and chemokine (C-X-C motif) receptor (CXCR)2 increased after TBI, and CXCL1 was mainly expressed in astrocytes, while CXCR2 was mainly expressed in neurons. Increased apoptosis of cortical nerve cells in the injured cortex was also found after TBI. Reduced nerve cell apoptosis with improved neurological function was observed after application of a CXCR2 antagonist. The expression of phospho-extracellular signal-regulated kinase (p-ERK), phospho-c-Jun N-terminal kinase (p-JNK) and p-NF-κB increased after TBI, and application of ERK, JNK and NF-κB inhibitors decreased expression of CXCL1 and CXCR2 in rats. We further found that HBO therapy down-regulated the expression of p-ERK, p-JNK, p-NF-κB, CXCL1, and CXCR2, and reduced nerve cell apoptosis, improved the neurological function of TBI rats, and ultimately alleviated the secondary injury. In conclusion, HBO therapy may exert neuroprotective effect by regulating the NF-κB/MAPKs (JNK and ERK)-CXCL1 inflammatory pathways following TBI, which probably provide the theoretical and experimental basis for the clinical application of HBO therapy in the treatment of TBI.

To evaluate the effects of hyperbaric oxygen (HBO) therapy in the management of chronic wound and observe the correlation between wound healing and CD34+ endothelial progenitor cells (EPCs). A total of 119 patients with chronic wound in lower extremities lasting > 3 months were recruited for this randomized, single-center, placebo-controlled clinical trial. The changes of CD34+ average count before and after HBO therapy were detected by flow cytometry (FACS). There were 97 patients on long-term HBO therapy and in 22 patients on hyperbaric air therapy as control group. The CD34/Scal-1+ and CD34/CXCR4 dual-positive populations of gated cell were determined respectively by FACs. The outcomes of two groups were compared. Treatment was administered within a single-place hyperbaric chamber for 90-min daily (session duration 120 min) for 5 days a week for 4 weeks (20 treatment sessions). The wound size decreased at the 4-week end point (62.7% ± 22.3% in the HBO group vs 34.4% ± 20.6% in the control group, P < 0.05). After 10 episodes of HBO therapies for chronic non-healing wound, the peripheral CD34+ EPCs average count rose from 0.24% ± 0.03% at pre-treatment to 1.32% ± 0.05% while the number was 1.75% ± 0.17% after 20 episodes of HBO (P < 0.05). Both were significantly different from that of the patients at pre-treatment. However the overall circulating white cell count was not significantly elevated. The CD34/Scal-1+ and CD34/CXCR4 dual-positive populations of gated cell in HBO group were 5.8 and 5.2 folds than those at pre-treatment respectively. The number of EPCs was positively correlated with wound healing in lower extremities (correlation coefficient 0.84; P < 0.01). Adjunctive treatment of HBO facilitates the healing of chronic non-healing wound in selected patients through the mobilization of EPCs.

This study was designed to determine if a) hyperbaric oxygen increases the tissue oxygenation of free flaps and b) verification of this effect is possible by using a recently validated and innovative method for two-dimensional pO₂ measurement (Luminescence lifetime imaging = LLI). Six patients with a free parascapular flap transplanted to the lower limb received hyperbaric oxygen (HBOT) therapy. The HBOT regimen consisted of treatment over 90 minutes with 100% O₂ (FiO₂ 1.0) at 240 kPa (Marx-Schema). The transcutaneous oxygen partial pressure (ptcO₂) was measured over the entire flap with the use of luminescence lifetime imaging (LLI) before and 30, 60, 120 minutes after treatment. The LLI is based on the oxygen dependent quenching of phosphorescence of the indicator dye platinum (II)-octaethyl-porphyrin implemented in a polystyrene sensor foil. In all six free flaps we could find a significant increase of tissue oxygen over the entire flap in form of increased R-values as well as subsequently calculated absolute ptcO₂ values over a period of 120 min after hyperbaric therapy. The ptcO₂ values increased significantly from 42.59 ± 1.11 Torr before to 81.14 ± 5.95 Torr after hyperbaric treatment (p < 0.001). Even after 2 hours the ptcO₂ values were significantly higher (83.45 ± 13.80 Torr) compared with values prior to HBOT (p < 0.006). The findings of this study demonstrated an increase of oxygen supply over the entire flap after hyperbaric oxygen therapy.

Graduated compression stockings (GCS) are one of the essential mechanical therapeutic approaches used in prevention and treatment of venous diseases. Pressure levels and gradient distribution are the two determined parameters influencing the performance of GCS products. However, the effects of GCS with different pressure profiles on venous function remain controversial in practical use. To determine the physiological effects of GCS with different pressure levels and gradient distribution profiles on the venous function of the lower extremities. At specific testing points along the long and short saphenous veins (LSV, SSV) and popliteal veins (PV) of the lower extremities, Doppler ultrasound techniques were used to examine venous cross-sectional areas (VA, cm(2)), the venous peak blood flow (PVpeak, cm/sec) and venous mean blood flow (PVmean, cm/sec) velocities in twelve female subjects wearing GCS with varying pressure profiles in a controlled laboratory environment. The Doppler examination was conducted three times during the 4-hour period (after wearing GCS for 1 minute, 70 minutes, and 170 minutes) in each subject. The pressure levels of GCS and duration of wear had statistically significant influences on the venous anatomy and venous haemodynamics. GCS with light, mild, moderate and strong pressures increased the popliteal PVpeak by 9.64%, 25.74%, 29.91% and 26.47%, respectively, and significantly decreased the VA. The GCS maintained these venous haemodynamics over time. No significant differences in blood flow were found between the mild, moderate and strong pressure GCS. The application of GCS with light and mild compression profiles appear to be effective in achieving a reduction in venous dilation and venous pooling, and improving venous return in the lower extremities. GCS with lighter pressures may be more suitable for subjects whose daily work requires long-term inactive standing or sitting, and GCS with mild pressure appear to be sufficient for most clinical applications.