Paul G. Harch, MD: Hyperbaric Oxygen Therapy and Coronavirus Application.

No Abstract Available.

Systematic review and dosage analysis: hyperbaric oxygen therapy efficacy in the treatment of posttraumatic stress disorder.

Background: Studies of hyperbaric oxygen therapy (HBOT) treatment of mild traumatic brain injury persistent postconcussion syndrome in military and civilian subjects have shown simultaneous improvement in posttraumatic stress disorder (PTSD) or PTSD symptoms, suggesting that HBOT may be an effective treatment for PTSD. This is a systematic review and dosage analysis of HBOT treatment of patients with PTSD symptoms. Methods: PubMed, CINAHL, and the Cochrane Systematic Review Database were searched from September 18 to November 23, 2023, for all adult clinical studies published in English on HBOT and PTSD. Randomized trials and studies with symptomatic outcomes were selected for final analysis and analyzed according to the dose of oxygen and barometric pressure on symptom outcomes. Outcome assessment was for statistically significant change and Reliable Change or Clinically Significant Change according to the National Center for PTSD Guidelines. Methodologic quality and bias were determined with the PEDro Scale. Results: Eight studies were included, all with < 75 subjects/study, total 393 subjects: seven randomized trials and one imaging case-controlled study. Six studies were on military subjects, one on civilian and military subjects, and one on civilians. Subjects were 3-450 months post trauma. Statistically significant symptomatic improvements, as well as Reliable Change or Clinically Significant changes, were achieved for patients treated with 40-60 HBOTS over a wide range of pressures from 1.3 to 2.0 ATA. There was a linear dose-response relationship for increased symptomatic improvement with increasing cumulative oxygen dose from 1002 to 11,400 atmosphere-minutes of oxygen. The greater symptomatic response was accompanied by a greater and severe reversible exacerbation of emotional symptoms at the highest oxygen doses in 30-39% of subjects. Other side effects were transient and minor. In three studies the symptomatic improvements were associated with functional and anatomic brain imaging changes. All 7 randomized trials were found to be of good-highest quality by PEDro scale scoring. Discussion: In multiple randomized and randomized controlled clinical trials HBOT demonstrated statistically significant symptomatic improvements, Reliable Changes, or Clinically Significant Changes in patients with PTSD symptoms or PTSD over a wide range of pressure and oxygen doses. The highest doses were associated with a severe reversible exacerbation of emotional symptoms in 30-39% of subjects. Symptomatic improvements were supported by correlative functional and microstructural imaging changes in PTSD-affected brain regions. The imaging findings and hyperbaric oxygen therapy effects indicate that PTSD can no longer be considered strictly a psychiatric disease.

Acute and chronic central nervous system oxidative stress/toxicity during hyperbaric oxygen treatment of subacute and chronic neurological conditions.

Introduction: Oxygen toxicity has been defined as acute central nervous system (CNS), acute pulmonary, and chronic pulmonary oxygen toxicity. This study identifies acute and chronic CNS oxygen toxicity under 2.0 atmospheres absolute (ATA) pressure of oxygen. Methods: The authors' medical records from September 29, 1989 to January 20, 2023 and correspondence to the authors (9/1994 to 1/20.2023) from patients with signs and/or symptoms historically identified as acute CNS oxygen toxicity and those with neurological deterioration receiving hyperbaric oxygen for neurological conditions were reviewed. Acute cases were those occurring with ≤5 HBOTs and chronic cases >5 HBOTs. Chronic cases were separated into those at 1.5 ATA, > 1.5 ATA, or < 1.5 ATA oxygen. Cumulative dose of oxygen in atmosphere-hours (AHs) was calculated at symptom onset. Results: Seven acute cases, average 4.0 ± 2.7 AHs, and 52 chronic cases were identified: 31 at 1.5 ATA (average 116 ± 106 AHs), 12 at >1.5 ATA (103 ± 74 AHs), and 9 at <1.5 ATA (114 ± 116 AHs). Second episodes occurred at 81 ± 55, 67 ± 49, and 22 ± 17 AHs, and three or more episodes at 25 ± 18, 83 ± 7.5, and 5.4 ± 6.0 AHs, respectively. Most cases were reversible. There was no difference between adults and children (p = 0.72). Acute intervention in cases (<3 months) was more sensitive than delayed intervention (21.1 ± 8.8 vs. 123 ± 102 AHs, p = 0.035). Outside sources reported one acute and two chronic exposure deaths and one patient institutionalized due to chronic oxygen toxicity. A withdrawal syndrome was also identified. Conclusion: Hyperbaric oxygen therapy-generated acute and chronic cases of CNS oxygen toxicity in chronic neurological conditions were identified at <2.0 ATA. Chronic CNS oxygen toxicity is idiosyncratic, unpredictable, and occurred at an average threshold of 103-116 AHs with wide variability. There was no difference between adults and children, but subacute cases were more sensitive than chronic intervention cases. When identified early it was reversible and an important aid in proper dosing of HBOT. If ignored permanent morbidity and mortality resulted with continued HBOT.

Serum microRNAs associated with concussion in football players.

Mild Traumatic Brain Injury (mild TBI)/concussion is a common sports injury, especially common in football players. Repeated concussions are thought to lead to long-term brain damage including chronic traumatic encephalopathy (CTE). With the worldwide growing interest in studying sport-related concussion the search for biomarkers for early diagnosis and progression of neuronal injury has also became priority. MicroRNAs are short, non-coding RNAs that regulate gene expression post-transcriptionally. Due to their high stability in biological fluids, microRNAs can serve as biomarkers in a variety of diseases including pathologies of the nervous system. In this exploratory study, we have evaluated changes in the expression of selected serum miRNAs in collegiate football players obtained during a full practice and game season. We found a miRNA signature that can distinguish with good specificity and sensitivity players with concussions from non-concussed players. Furthermore, we found miRNAs associated with the acute phase (let-7c-5p, miR-16-5p, miR-181c-5p, miR-146a-5p, miR-154-5p, miR-431-5p, miR-151a-5p, miR-181d-5p, miR-487b-3p, miR-377-3p, miR-17-5p, miR-22-3p, and miR-126-5p) and those whose changes persist up to 4 months after concussion (miR-17-5p and miR-22-3p).

Systematic Review and Dosage Analysis: Hyperbaric Oxygen Therapy Efficacy in Mild Traumatic Brain Injury Persistent Postconcussion Syndrome.

Background: Mild traumatic brain injury results in over 15% of patients progressing to Persistent Postconcussion Syndrome, a condition with significant consequences and limited treatment options. Hyperbaric oxygen therapy has been applied to Persistent Postconcussion Syndrome with conflicting results based on its historical understanding/definition as a disease-specific therapy. This is a systematic review of the evidence for hyperbaric oxygen therapy (HBOT) in Persistent Postconcussion Syndrome using a dose-analysis that is based on the scientific definition of hyperbaric oxygen therapy as a dual-component drug composed of increased barometric pressure and hyperoxia. Methods: In this review, PubMed, CINAHL, and the Cochrane Systematic Review Database were searched from August 8-22, 2021 for all adult clinical studies published in English on hyperbaric oxygen therapy in mild traumatic brain injury Persistent Postconcussion Syndrome (symptoms present at least 3 months). Randomized trials and studies with symptomatic and/or cognitive outcomes were selected for final analysis. Randomized trials included those with no-treatment control groups or control groups defined by either the historical or scientific definition. Studies were analyzed according to the dose of oxygen and barometric pressure and classified as Levels 1-5 based on significant immediate post-treatment symptoms or cognitive outcomes compared to control groups. Levels of evidence classifications were made according to the Centre for Evidence-Based Medicine and a practice recommendation according to the American Society of Plastic Surgeons. Methodologic quality and bias were assessed according to the PEDro Scale. Results: Eleven studies were included: six randomized trials, one case-controlled study, one case series, and three case reports. Whether analyzed by oxygen, pressure, or composite oxygen and pressure dose of hyperbaric therapy statistically significant symptomatic and cognitive improvements or cognitive improvements alone were achieved for patients treated with 40 HBOTS at 1.5 atmospheres absolute (ATA) (four randomized trials). Symptoms were also improved with 30 treatments at 1.3 ATA air (one study), positive and negative results were obtained at 1.2 ATA air (one positive and one negative study), and negative results in one study at 2.4 ATA oxygen. All studies involved <75 subjects/study. Minimal bias was present in four randomized trials and greater bias in 2. Conclusion: In multiple randomized and randomized controlled studies HBOT at 1.5 ATA oxygen demonstrated statistically significant symptomatic and cognitive or cognitive improvements alone in patients with mild traumatic brain injury Persistent Postconcussion Syndrome. Positive and negative results occurred at lower and higher doses of oxygen and pressure. Increased pressure within a narrow range appears to be the more important effect than increased oxygen which is effective over a broad range. Improvements were greater when patients had comorbid Post Traumatic Stress Disorder. Despite small sample sizes, the 1.5 ATA HBOT studies meet the Centre for Evidence-Based Medicine Level 1 criteria and an American Society of Plastic Surgeons Class A Recommendation for HBOT treatment of mild traumatic brain injury persistent postconcussion syndrome.

Hyperbaric oxygen therapy for mild traumatic brain injury persistent postconcussion syndrome: a randomized controlled trial.

Persistent postconcussion syndrome (PPCS) after mild traumatic brain injury (mTBI) is a significant public health and military problem for which there is limited treatment evidence. The aim of this study was to determine whether forty 150 kPa hyperbaric oxygen therapies (HBOTs) can improve symptoms and cognitive function in subjects with the PPCS of mTBI, using a randomized controlled crossover design with 2-month follow-up. Sixty-three civilian and military subjects with mTBI/PPCS were randomized to either 40 HBOTs at 150 kPa/60 minutes, once daily, 5 days per week in 8 weeks or an equivalent no-treatment control period. The Control Group was then crossed over to HBOT. Subjects underwent symptom, neuropsychological, and psychological testing, before and after treatment or control with retesting 2 months after the 40th HBOT. Fifty subjects completed the protocol with primary outcome testing. HBOT subjects experienced significant improvements in Neurobehavioral Symptom Inventory, Memory Index, Automated Neuropsychological Assessment Metrics, Hamilton Depression Scale, Hamilton Anxiety Scale, Post-Traumatic Stress Disorder Checklist, Pittsburgh Sleep Quality Index, and Quality Of Life after Brain Injury compared to the Control Group. After crossing over to HBOT the Control Group experienced near-identical significant improvements. Further improvements were experienced by both groups during the 2-month follow-up period. These data indicate that 40 HBOTs at 150 kPa/60 minutes demonstrated statistically significant improvements in postconcussion and Post-Traumatic Stress Disorder symptoms, memory, cognitive functions, depression, anxiety, sleep, and quality of life in civilian and military subjects with mTBI/PPCS compared to controls. Improvements persisted at least 2 months after the 40th HBOT. The study was registered on ClinicalTrials.gov (NCT02089594) on March 18, 2014 and with the U.S. Food and Drug Administration under Investigational New Drug #113823. The Institutional Review Boards of the United States Army Medical Research and Materiel Command Office of Research Protections Human Research Protection Office and the Louisiana State University School of Medicine (approval No. 7381) approved the study on May 13, 2014 and December 20, 2013, respectively.

Hyperbaric oxygen improves rate of return of spontaneous circulation after prolonged normothermic porcine cardiopulmonary arrest.

AIM: This controlled, prospective, randomized porcine study tests the hypothesis that high-dose hyperbaric oxygen (HDHBO2) compared with normobaric oxygen (NBO2) or standard-dose hyperbaric oxygen (SDHBO2), improves return of sustained spontaneous circulation (ROSC) after a normothermic, normobaric, 25-min, non-intervened-upon cardiopulmonary arrest. The study incorporated a direct mechanical ventricular assist device (DMVAD) for open chest continuous cardiac compressions (OCCC) to assist advanced cardiac life support (ACLS). The experiment demonstrates a dose response to oxygen concentration in the breathing mix used in resuscitative ventilation. MATERIALS AND METHODS: Male pigs (average 30kg weight) underwent a 25-min, normothermic, non-intervened-upon cardiopulmonary arrest. Following arrest all animals were ventilated with 100% oxygen and were subjected to OCCC, incorporating DMVAD-aided ACLS. The animals so treated were randomized to be in one of three groups, with six animals in each group. The NBO2 group remained at 1.0 atmosphere absolute (ATA), while the SDHBO2 and HDHBO2 groups were initially placed at 1.9 and 4.0ATA, respectively. Uniform, but not American Heart Association (AHA) protocol, ACLS was maintained as needed over the ensuing 2h for all animals in all groups. At the end of 2h, the animals were euthanized. RESULTS: Continuously sustained ROSC (mean arterial pressure > or =50mmHg at all times), without the need of the pump assist over the 2-h resuscitation attempt that followed the 25-min arrest, occurred in four out of six animals in the HDHBO2 group, and in none of the animals in the NBO2 or SBHBO2 groups (p< or =0.001). CONCLUSIONS: Our results show significantly sustained ROSC using HDHBO2 to resuscitate swine after a 25-min, non-intervened-upon, normothermic cardiopulmonary arrest. These results could not be achieved using NBO2 or SDHBO2.

Hyperbaric oxygen therapy for Alzheimer's dementia with positron emission tomography imaging: a case report.

A 58-year-old female was diagnosed with Alzheimer's dementia (AD) which was rapidly progressive in the 8 months prior to initiation of hyperbaric oxygen therapy (HBOT). 18Fluorodeoxyglucose (18FDG) positron emission tomography (PET) brain imaging demonstrated global and typical metabolic deficits in AD (posterior temporal-parietal watershed and cingulate areas). An 8-week course of HBOT reversed the patient's symptomatic decline. Repeat PET imaging demonstrated a corresponding 6.5-38% regional and global increase in brain metabolism, including increased metabolism in the typical AD diagnostic areas of the brain. Continued HBOT in conjunction with standard pharmacotherapy maintained the patient's symptomatic level of function over an ensuing 22 months. This is the first reported case of simultaneous HBOT-induced symptomatic and 18FDG PET documented improvement of brain metabolism in AD and suggests an effect on global pathology in AD.

Hyperbaric oxygen therapy improves spatial learning and memory in a rat model of chronic traumatic brain injury.

In the present experiment we use a rat model of traumatic brain injury to evaluate the ability of low-pressure hyperbaric oxygen therapy (HBOT) to improve behavioral and neurobiological outcomes. The study employed an adaptation of the focal cortical contusion model. 64 Male Long-Evans rats received unilateral cortical contusion and were tested in the Morris Water Task (MWT) 31-33 days post injury. Rats were divided into three groups: an untreated control group (N=22), an HBOT treatment group (N=19) and a sham-treated normobaric air group (N=23). The HBOT group received 80 bid, 7 days/week 1.5 ATA/90-min HBOTs and the sham-treated normobaric air group the identical schedule of air treatments using a sham hyperbaric pressurization. All rats were subsequently retested in the MWT. After testing all rats were euthanized. Blood vessel density was measured bilaterally in hippocampus using a diaminobenzadine stain and was correlated with MWT performance. HBOT caused an increase in vascular density in the injured hippocampus (p<0.001) and an associated improvement in spatial learning (p<0.001) compared to the control groups. The increased vascular density and improved MWT in the HBOT group were highly correlated (p<0.001). In conclusion, a 40-day series of 80 low-pressure HBOTs caused an increase in contused hippocampus vascular density and an associated improvement in cognitive function. These findings reaffirm the clinical experience of HBOT-treated patients with chronic traumatic brain injury.

Subacute normobaric oxygen and hyperbaric oxygen therapy in drowning, reversal of brain volume loss: a case report.

A 2-year-old girl experienced cardiac arrest after cold water drowning. Magnetic resonance imaging (MRI) showed deep gray matter injury on day 4 and cerebral atrophy with gray and white matter loss on day 32. Patient had no speech, gait, or responsiveness to commands on day 48 at hospital discharge. She received normobaric 100% oxygen treatment (2 L/minute for 45 minutes by nasal cannula, twice/day) since day 56 and then hyperbaric oxygen treatment (HBOT) at 1.3 atmosphere absolute (131.7 kPa) air/45 minutes, 5 days/week for 40 sessions since day 79; visually apparent and/or physical examination-documented neurological improvement occurred upon initiating each therapy. After HBOT, the patient had normal speech and cognition, assisted gait, residual fine motor and temperament deficits. MRI at 5 months after injury and 27 days after HBOT showed near-normalization of ventricles and reversal of atrophy. Subacute normobaric oxygen and HBOT were able to restore drowning-induced cortical gray matter and white matter loss, as documented by sequential MRI, and simultaneous neurological function, as documented by video and physical examinations.

Case control study: hyperbaric oxygen treatment of mild traumatic brain injury persistent post-concussion syndrome and post-traumatic stress disorder.

Mild traumatic brain injury (TBI) persistent post-concussion syndrome (PPCS) and post-traumatic stress disorder (PTSD) are epidemic in United States Iraq and Afghanistan War veterans. Treatment of the combined diagnoses is limited. The aim of this study is to assess safety, feasibility, and effectiveness of hyperbaric oxygen treatments (HBOT) for mild TBI PPCS and PTSD. Thirty military subjects aged 18-65 with PPCS with or without PTSD and from one or more blast-induced mild-moderate traumatic brain injuries that were a minimum of 1 year old and occurred after 9/11/2001 were studied. The measures included symptom lists, physical exam, neuropsychological and psychological testing on 29 subjects (1 dropout) and SPECT brain imaging pre and post HBOT. Comparison was made using SPECT imaging on 29 matched Controls. Side effects (30 subjects) experienced due to the HBOT: reversible middle ear barotrauma (n = 6), transient deterioration in symptoms (n = 7), reversible bronchospasm (n = 1), and increased anxiety (n = 2; not related to confinement); unrelated to HBOT: ureterolithiasis (n = 1), chest pain (n = 2). Significant improvement (29 subjects) was seen in neurological exam, symptoms, intelligence quotient, memory, measures of attention, dominant hand motor speed and dexterity, quality of life, general anxiety, PTSD, depression (including reduction in suicidal ideation), and reduced psychoactive medication usage. At 6-month follow-up subjects reported further symptomatic improvement. Compared to Controls the subjects' SPECT was significantly abnormal, significantly improved after 1 and 40 treatments, and became statistically indistinguishable from Controls in 75% of abnormal areas. HBOT was found to be safe and significantly effective for veterans with mild to moderate TBI PPCS with PTSD in all four outcome domains: clinical medicine, neuropsychology, psychology, and SPECT imaging. Veterans also experienced a significant reduction in suicidal ideation and reduction in psychoactive medication use.

Hyperbaric oxygen in chronic traumatic brain injury: oxygen, pressure, and gene therapy.

Hyperbaric oxygen therapy is a treatment for wounds in any location and of any duration that has been misunderstood for 353 years. Since 2008 it has been applied to the persistent post-concussion syndrome of mild traumatic brain injury by civilian and later military researchers with apparent conflicting results. The civilian studies are positive and the military-funded studies are a mixture of misinterpreted positive data, indeterminate data, and negative data. This has confused the medical, academic, and lay communities. The source of the confusion is a fundamental misunderstanding of the definition, principles, and mechanisms of action of hyperbaric oxygen therapy. This article argues that the traditional definition of hyperbaric oxygen therapy is arbitrary. The article establishes a scientific definition of hyperbaric oxygen therapy as a wound-healing therapy of combined increased atmospheric pressure and pressure of oxygen over ambient atmospheric pressure and pressure of oxygen whose main mechanisms of action are gene-mediated. Hyperbaric oxygen therapy exerts its wound-healing effects by expression and suppression of thousands of genes. The dominant gene actions are upregulation of trophic and anti-inflammatory genes and down-regulation of pro-inflammatory and apoptotic genes. The combination of genes affected depends on the different combinations of total pressure and pressure of oxygen. Understanding that hyperbaric oxygen therapy is a pressure and oxygen dose-dependent gene therapy allows for reconciliation of the conflicting TBI study results as outcomes of different doses of pressure and oxygen.

Decompression illness in divers: a review of the literature.

BACKGROUND: Neurologists may be consulted to diagnose and treat the severe neurologic injuries that can occur in divers with decompression illness (DCI). REVIEW SUMMARY: Subclinical bubbles form during normal diving activity. DCI, a diffuse and multifocal process, results when bubbles cause symptoms by exerting mass effect in tissues, or obstructing venous or arterial flow. The lower thoracic spinal cord is a commonly affected area of the central nervous system. The most commonly described form of brain DCI is cerebral arterial gas embolism with middle cerebral artery or vertebrobasilar distribution involvement. Bubbles exert secondary damage to the vascular endothelium, causing activation of numerous biochemical cascades. CONCLUSIONS: Divers can develop DCI on very short dives or in shallow water, even when adhering to protocols. DCI should be strongly considered when divers experience pain after diving. Any neurologic symptoms after a dive are abnormal and should be attributed to DCI. Even doubtful cases should be treated immediately with hyperbaric oxygen (HBO), after a chest x-ray to rule out pneumothorax. The Divers Alert Network should be contacted for emergency consultation. Delay to treatment can worsen outcome; however, the overwhelming majority of divers respond to HBO even days to weeks after injury. Although DCI is a clinical diagnosis, magnetic resonance imaging, somatosensory evoked potentials, single-photon emission tomography, and neuropsychologic testing help to document disease and monitor response to therapy. Divers should be treated with HBO until they reach a clinical plateau. Complete relief of symptoms occurs in 50% to 70% of divers; 30% have partial relief.

A phase I study of low-pressure hyperbaric oxygen therapy for blast-induced post-concussion syndrome and post-traumatic stress disorder.

This is a preliminary report on the safety and efficacy of 1.5 ATA hyperbaric oxygen therapy (HBOT) in military subjects with chronic blast-induced mild to moderate traumatic brain injury (TBI)/post-concussion syndrome (PCS) and post-traumatic stress disorder (PTSD). Sixteen military subjects received 40 1.5 ATA/60 min HBOT sessions in 30 days. Symptoms, physical and neurological exams, SPECT brain imaging, and neuropsychological and psychological testing were completed before and within 1 week after treatment. Subjects experienced reversible middle ear barotrauma (5), transient deterioration in symptoms (4), and reversible bronchospasm (1); one subject withdrew. Post-treatment testing demonstrated significant improvement in: symptoms, neurological exam, full-scale IQ (+14.8 points; p<0.001), WMS IV Delayed Memory (p=0.026), WMS-IV Working Memory (p=0.003), Stroop Test (p<0.001), TOVA Impulsivity (p=0.041), TOVA Variability (p=0.045), Grooved Pegboard (p=0.028), PCS symptoms (Rivermead PCSQ: p=0.0002), PTSD symptoms (PCL-M: p<0.001), depression (PHQ-9: p<0.001), anxiety (GAD-7: p=0.007), quality of life (MPQoL: p=0.003), and self-report of percent of normal (p<0.001), SPECT coefficient of variation in all white matter and some gray matter ROIs after the first HBOT, and in half of white matter ROIs after 40 HBOT sessions, and SPECT statistical parametric mapping analysis (diffuse improvements in regional cerebral blood flow after 1 and 40 HBOT sessions). Forty 1.5 ATA HBOT sessions in 1 month was safe in a military cohort with chronic blast-induced PCS and PTSD. Significant improvements occurred in symptoms, abnormal physical exam findings, cognitive testing, and quality-of-life measurements, with concomitant significant improvements in SPECT.

Low pressure hyperbaric oxygen therapy and SPECT brain imaging in the treatment of blast-induced chronic traumatic brain injury (post-concussion syndrome) and post traumatic stress disorder: a case report.

A 25-year-old male military veteran presented with diagnoses of post concussion syndrome and post traumatic stress disorder three years after loss of consciousness from an explosion in combat. The patient underwent single photon emission computed tomography brain blood flow imaging before and after a block of thirty-nine 1.5 atmospheres absolute hyperbaric oxygen treatments. The patient experienced a permanent marked improvement in his post-concussive symptoms, physical exam findings, and brain blood flow. In addition, he experienced a complete resolution of post-traumatic stress disorder symptoms. After treatment he became and has remained employed for eight consecutive months. This case suggests a novel treatment for the combined diagnoses of blast-induced post-concussion syndrome and post-traumatic stress disorder.