Dysbarism: An Overview of an Unusual Medical Emergency

Dysbarism is a general term which includes the signs and symptoms that can manifest when the body is subject to an increase or a decrease in the atmospheric pressure which occurs either at a rate or duration exceeding the capacity of the body to adapt safely. In the following review, we take dysbarisms into account for our analysis. Starting from the underlying physical laws, we will deal with the pathologies that can develop in the most frequently affected areas of the body, as the atmospheric pressure varies when acclimatization fails. Manifestations of dysbarism range from itching and minor pain to neurological symptoms, cardiac collapse, and death. Overall, four clinical pictures can occur: decompression illness, barotrauma, inert gas narcosis, and oxygen toxicity. We will then review the clinical manifestations and illustrate some hints of therapy. We will first introduce the two forms of decompression sickness. In the next part, we will review the barotrauma, compression, and decompression. The last three parts will be dedicated to gas embolism, inert gas narcosis, and oxygen toxicity. Such an approach is critical for the effective treatment of patients in a hostile environment, or treatment in the emergency room after exposure to extreme physical or environmental factors.

Seizures Caused by Exposure to Hyperbaric Oxygen in Rats Can Be Predicted by Early Changes in Electrodermal Activity

Hyperbaric oxygen (HBO2) is breathed during undersea operations and in hyperbaric medicine. However, breathing HBO2 by divers and patients increases the risk of central nervous system oxygen toxicity (CNS-OT), which ultimately manifests as sympathetic stimulation producing tachycardia and hypertension, hyperventilation, and ultimately generalized seizures and cardiogenic pulmonary edema. In this study, we have tested the hypothesis that changes in electrodermal activity (EDA), a measure of sympathetic nervous system activation, precedes seizures in rats breathing 5 atmospheres absolute (ATA) HBO2. Radio telemetry and a rodent tether apparatus were adapted for use inside a sealed hyperbaric chamber. The tethered rat was free to move inside a ventilated animal chamber that was flushed with air or 100% O2. The animal chamber and hyperbaric chamber (air) were pressurized in parallel at ~1 atmosphere/min. EDA activity was recorded simultaneously with cortical electroencephalogram (EEG) activity, core body temperature, and ambient pressure. We have captured the dynamics of EDA using time-varying spectral analysis of raw EDA (TVSymp), previously developed as a tool for sympathetic tone assessment in humans, adjusted to detect the dynamic changes of EDA in rats that occur prior to onset of CNS-OT seizures. The results show that a significant increase in the amplitude of TVSymp values derived from EDA recordings occurs on average (±SD) 1.9 ± 1.6 min before HBO2-induced seizures. These results, if corroborated in humans, support the use of changes in TVSymp activity as an early “physio-marker” of impending and potentially fatal seizures in divers and patients.

Hyperoxemia among Pediatric Intensive Care Unit Patients Receiving Oxygen Therapy

Supratherapeutic oxygen levels consistently cause oxygen toxicity in the lungs and other organs. The prevalence and severity of hyperoxemia among pediatric intensive care unit (PICU) patients remain unknown. This was the first study to examine the prevalence and duration of hyperoxemia in PICU patients receiving oxygen therapy. This is a retrospective chart review. This was performed in a setting of 36-bed PICU in a quaternary-care children's hospital. All the patients were children aged <18 years, admitted to the PICU for ≥24 hours, receiving oxygen therapy for ≥12 hours who had at least one arterial blood gas during this time.There was no intervention. Of 5,251 patients admitted to the PICU, 614 were included in the study. On average, these patients received oxygen therapy for 91% of their time in the PICU and remained hyperoxemic, as measured by pulse oximetry, for 65% of their time on oxygen therapy. Patients on oxygen therapy remained hyperoxemic for a median of 38 hours per patient and only 1.1% of patients did not experience any hyperoxemia. Most of the time (87.5%) patients received oxygen therapy through a fraction of inspired oxygen (FiO2)-adjustable device. Mean FiO2 on noninvasive support was 0.56 and on invasive support was 0.37. Mean partial pressure of oxygen (PaO2) on oxygen therapy was 108.7 torr and 3,037 (42.1%) of PaO2 measurements were >100 torr. Despite relatively low FiO2, PICU patients receiving oxygen therapy are commonly exposed to prolonged hyperoxemia, which may contribute to ongoing organ injury.

Common Uses and Adverse Effects of Hyperbaric Oxygen Therapy in a Cohort of Small Animal Patients: A Retrospective Analysis of 2,792 Treatment Sessions

Hyperbaric oxygen therapy (HBOT) is commonly utilized for various human conditions with a low incidence of major adverse effects (0.002–0.035%). Despite growing use in veterinary patients, there remains a paucity of literature describing its use and associated complications. The purpose of this study was to report clinical use of HBOT in small animals and identify the rate of major adverse events at a university teaching hospital. Electronic medical records were searched for small animals receiving HBOT between November 2012 and February 2020. Data extracted from the medical records included signalment, treatment indication, and adverse events. Treatment sessions totaled 2,792 in 542 dogs, 24 cats, and 10 pocket pets and exotics. Common indications included neurologic injuries (50.4%), tissue healing (31.4%), control of oomycete infection (5.5%), neoplasia or post-radiation injury (5.4%), and various miscellaneous conditions (7.4%). Observed minor adverse events included agitation in two dogs and vomiting in three dogs. The most common major adverse event was central nervous system (CNS) oxygen toxicity in 19 dogs. Central nervous system oxygen toxicity, manifesting as focal or generalized seizures, occurred in 0.7% of treatment sessions, with increasing age (p = 0.01) and female sex (p = 0.01) identified as risk factors. One dog developed pulmonary edema following HBOT which is a reported adverse event in humans or may have been a manifestation of progression of the dog's underlying disease. No adverse events were noted in cats or other species. In conclusion, HBOT appeared safe across various indications, although oxygen toxicity affecting the CNS was higher than reports in humans. Future prospective, randomized, controlled trials should evaluate specific clinical indications and outcomes.

Oxygen Toxicity to the Immature Lung—Part I: Pathomechanistic Understanding and Preclinical Perspectives

In utero, the fetus and its lungs develop in a hypoxic environment, where HIF-1α and VEGFA signaling constitute major determinants of further development. Disruption of this homeostasis after preterm delivery and extrauterine exposure to high fractions of oxygen are among the key events leading to bronchopulmonary dysplasia (BPD). Reactive oxygen species (ROS) production constitutes the initial driver of pulmonary inflammation and cell death, altered gene expression, and vasoconstriction, leading to the distortion of further lung development. From preclinical studies mainly performed on rodents over the past two decades, the deleterious effects of oxygen toxicity and the injurious insults and downstream cascades arising from ROS production are well recognized. This article provides a concise overview of disease drivers and different therapeutic approaches that have been successfully tested within experimental models. Despite current studies, clinical researchers are still faced with an unmet clinical need, and many of these strategies have not proven to be equally effective in clinical trials. In light of this challenge, adapting experimental models to the complexity of the clinical situation and pursuing new directions constitute appropriate actions to overcome this dilemma. Our review intends to stimulate research activities towards the understanding of an important issue of immature lung injury.

Oxygen Toxicity to the Immature Lung—Part II: The Unmet Clinical Need for Causal Therapy

Oxygen toxicity continues to be one of the inevitable injuries to the immature lung. Reactive oxygen species (ROS) production is the initial step leading to lung injury and, subsequently, the development of bronchopulmonary dysplasia (BPD). Today, BPD remains the most important disease burden following preterm delivery and results in life-long restrictions in lung function and further important health sequelae. Despite the tremendous progress in the pathomechanistic understanding derived from preclinical models, the clinical needs for preventive or curative therapies remain unmet. This review summarizes the clinical progress on guiding oxygen delivery to the preterm infant and elaborates future directions of research that need to take into account both hyperoxia and hypoxia as ROS sources and BPD drivers. Many strategies have been tested within clinical trials based on the mechanistic understanding of ROS actions, but most have failed to prove efficacy. The majority of these studies were tested in an era before the latest modes of non-invasive respiratory support and surfactant application were introduced or were not appropriately powered. A comprehensive re-evaluation of enzymatic, antioxidant, and anti-inflammatory therapies to prevent ROS injury is therefore indispensable. Strategies will only succeed if they are applied in a timely and vigorous manner and with the appropriate outcome measures.

Application of Ginsenoside-Rg1 Could Not Ameliorate The Hyperoxic-Induced Vascular Endothelial Oxidative Stress and Apoptosis

Background: Oxygen therapy is necessary to preterm infants with respiratory distress. However, hyperoxia may cause bronchopulmonary dysplasia and retinopathy of prematurity due to suppression of vasogenesis and increase of cell death. Ginsenoside-Rg1, one of the active components of Ginsen, is shown as a proangiogenic factor of vascular endothelial cells. We evaluated whether application of Ginsenoside-Rg1 is able to improve hyperoxic-induced vascular endothelium injury.Materials and methods: Human umbilical vein endothelial cells (HUVECs) were cultured under room air and 60% oxygen for 72 hours, respectively. Gensenoside-Rg1 was added to the medium at 0, 75, 150, 300nM. HUVECs proliferation, oxidative stress and apoptosis under normoxic and hyperoxic conditions were assayed by Western Blot.Results: Under hyperoxia (60% O2), HUVECs proliferation and levels of vascular endothelial growth factor (VEGF) were significantly decreased after ginsenoside-Rg1 treatment. Interestingly, both levels of glucocorticoid receptor (GR) and glutathione peroxidase (GPx) were increased after 72 hr Ginsenoside-Rg1 treatment, but no changed under room air control. The levels of oxidative stress-induced Bax and cytochrome c and apoptosis-related active caspase 3 and poly ADP-ribose polymerase were significantly increased after ginsenoside-Rg1 treatment under hyperoxic condition.Discussion and conclusion: In HUVECs model, Ginsenoside-Rg1 is unable to overcome the major hyperoxic-induced vascular endothelium injury. It might aggravate oxidative stress and endothelial apoptosis caused by oxygen toxicity. However, both elevated levels of GR and GPx indicate that Ginsenoside-Rg1 could be involved in vascular signaling and the regulation of oxidative stress under hyperoxia. Further investigation of Rg1 effects under hyperoxia is required.