Volatile Organic Compounds in Cellular Headspace after Hyperbaric Oxygen Exposure: An In Vitro Pilot Study.

Volatile organic compounds (VOCs) might be associated with pulmonary oxygen toxicity (POT). This pilot study aims to identify VOCs linked to oxidative stress employing an in vitro model of alveolar basal epithelial cells exposed to hyperbaric and hyperoxic conditions. In addition, the feasibility of this in vitro model for POT biomarker research was evaluated. The hyperbaric exposure protocol, similar to the U.S. Navy Treatment Table 6, was conducted on human alveolar basal epithelial cells, and the headspace VOCs were analyzed using gas chromatography-mass spectrometry. Three compounds (nonane [p = 0.005], octanal [p = 0.009], and decane [p = 0.018]), of which nonane and decane were also identified in a previous in vivo study with similar hyperbaric exposure, varied significantly between the intervention group which was exposed to 100% oxygen and the control group which was exposed to compressed air. VOC signal intensities were lower in the intervention group, but cellular stress markers (IL8 and LDH) confirmed increased stress and injury in the intervention group. Despite the observed reductions in compound expression, the model holds promise for POT biomarker exploration, emphasizing the need for further investigation into the complex relationship between VOCs and oxidative stress.

How fit are military hyperbaric personnel after an asymptomatic or mild symptomatic COVID-19 infection? A retrospective study.

INTRODUCTION: In the diving community there is a special need to know if asymptomatic or mild COVID-19 disease impacts the cardiopulmonary functioning of individuals with occupational exposure to extreme environments. To date, no controlled studies have been conducted comparing COVID-19-infected hyperbaric employees and non-COVID-19-infected peers in a military setting. METHODS: Between June 2020 and June 2021, healthy, hyperbaric, military personnel aged between 18 and 54 years old, who had recovered from asymptomatic or subclinical COVID-19 disease at least one month earlier, were analysed. Non-COVID-infected peers with medical assessments during the same period were used as the control group. Somatometry, spirometry, VO2 max, and DLCO were measured for each group. RESULTS: No clinically relevant differences in somatometry, lung function tests, and exercise testing were found between the COVID-19 group and the controls. However, the percentage of individuals with a decrease in estimated VO2-max of 10% or more was significantly greater in the COVID group than in the control group (24 vs. 7.8%, P = 0.004). CONCLUSIONS: After asymptomatic or mild symptomatic COVID-19 infections, military hyperbaric employees are as fit as those who had not encountered COVID-19. As this research was based on a military population, it cannot be extrapolated to a nonmilitary population. Further studies in nonmilitary populations are necessary to determine the medical relevance of the present findings.

Analysis of Volatile Organic Compounds in Exhaled Breath Following a COMEX-30 Treatment Table.

The COMEX-30 hyperbaric treatment table is used to manage decompression sickness in divers but may result in pulmonary oxygen toxicity (POT). Volatile organic compounds (VOCs) in exhaled breath are early markers of hyperoxic stress that may be linked to POT. The present study assessed whether VOCs following COMEX-30 treatment are early markers of hyperoxic stress and/or POT in ten healthy, nonsmoking volunteers. Because more oxygen is inhaled during COMEX-30 treatment than with other treatment tables, this study hypothesized that VOCs exhaled following COMEX-30 treatment are indicators of POT. Breath samples were collected before and 0.5, 2, and 4 h after COMEX-30 treatment. All subjects were followed-up for signs of POT or other symptoms. Nine compounds were identified, with four (nonanal, decanal, ethyl acetate, and tridecane) increasing 33-500% in intensity from before to after COMEX-30 treatment. Seven subjects reported pulmonary symptoms, five reported out-of-proportion tiredness and transient ear fullness, and four had signs of mild dehydration. All VOCs identified following COMEX-30 treatment have been associated with inflammatory responses or pulmonary diseases, such as asthma or lung cancer. Because most subjects reported transient pulmonary symptoms reflecting early-stage POT, the identified VOCs are likely markers of POT, not just hyperbaric hyperoxic exposure.

Volatile Organic Compounds Frequently Identified after Hyperbaric Hyperoxic Exposure: The VAPOR Library.

Diving or hyperbaric oxygen therapy with increased partial pressures of oxygen (pO2) can have adverse effects such as central nervous system oxygen toxicity or pulmonary oxygen toxicity (POT). Prevention of POT has been a topic of interest for several decades. One of the most promising techniques to determine early signs of POT is the analysis of volatile organic compounds (VOCs) in exhaled breath. We reanalyzed the data of five studies to compose a library of potential exhaled markers for the early detection of POT. GC-MS data from five hyperbaric hyperoxic studies were collected. Wilcoxon signed-rank tests were used to compare baseline- and postexposure measurements; all ion fragments that significantly varied were compared by similarity using the National Institute of Standards and Technology (NIST) library. All identified molecules were cross-referenced with open-source databases and other scientific publications on VOCs to exclude compounds that occurred as a result of contamination, and to identify the compounds most likely to occur due to hyperbaric hyperoxic exposure. After identification and removal of contaminants, 29 compounds were included in the library. This library of hyperbaric hyperoxic-related VOCs can help to advance the development of an early noninvasive marker of POT. It enables validation by others who use more targeted MS-related techniques, instead of full-scale GC-MS, for their exhaled VOC research.

Pulmonary Oxygen Toxicity Through Exhaled Breath Markers After Hyperbaric Oxygen Treatment Table 6.

Introduction: The hyperbaric oxygen treatment table 6 (TT6) is widely used to manage dysbaric illnesses in divers and iatrogenic gas emboli in patients after surgery and other interventional procedures. These treatment tables can have adverse effects, such as pulmonary oxygen toxicity (POT). It is caused by reactive oxygen species' damaging effect in lung tissue and is often experienced after multiple days of therapy. The subclinical pulmonary effects have not been determined. The primary aim of this study was to measure volatile organic compounds (VOCs) in breath, indicative of subclinical POT after a TT6. Since the exposure would be limited, the secondary aim of this study was to determine whether these VOCs decreased to baseline levels within a few hours. Methods: Fourteen healthy, non-smoking volunteers from the Royal Netherlands Navy underwent a TT6 at the Amsterdam University Medical Center-location AMC. Breath samples for GC-MS analysis were collected before the TT6 and 30 min, 2 and 4 h after finishing. The concentrations of ions before and after exposure were compared by Wilcoxon signed-rank tests. The VOCs were identified by comparing the chromatograms with the NIST library. Compound intensities over time were tested using Friedman tests, with Wilcoxon signed-rank tests and Bonferroni corrections used for post hoc analyses. Results: Univariate analyses identified 11 compounds. Five compounds, isoprene, decane, nonane, nonanal and dodecane, showed significant changes after the Friedman test. Isoprene demonstrated a significant increase at 30 min after exposure and a subsequent decrease at 2 h. Other compounds remained constant, but declined significantly 4 h after exposure. Discussion and Conclusion: The identified VOCs consisted mainly of (methyl) alkanes, which may be generated by peroxidation of cell membranes. Other compounds may be linked to inflammatory processes, oxidative stress responses or cellular metabolism. The hypothesis, that exhaled VOCs would increase after hyperbaric exposure as an indicator of subclinical POT, was not fulfilled, except for isoprene. Hence, no evident signs of POT or subclinical pulmonary damage were detected after a TT6. Further studies on individuals recently exposed to pulmonary irritants, such as divers and individuals exposed to other hyperbaric treatment regimens, are needed.

Perioperative Hyperoxyphobia: Justified or Not? Benefits and Harms of Hyperoxia during Surgery.

The use of an inspiratory oxygen fraction of 0.80 during surgery is a topic of ongoing debate. Opponents claim that increased oxidative stress, atelectasis, and impaired oxygen delivery due to hyperoxic vasoconstriction are detrimental. Proponents point to the beneficial effects on the incidence of surgical site infections and postoperative nausea and vomiting. Also, hyperoxygenation is thought to extend the safety margin in case of acute intraoperative emergencies. This review provides a comprehensive risk-benefit analysis for the use of perioperative hyperoxia in noncritically ill adults based on clinical evidence and supported by physiological deduction where needed. Data from the field of hyperbaric medicine, as a model of extreme hyperoxygenation, are extrapolated to the perioperative setting. We ultimately conclude that current evidence is in favour of hyperoxia in noncritically ill intubated adult surgical patients.

Routine Chest X-Rays Are Inaccurate in Detecting Relevant Intrapulmonary Anomalies During Medical Assessments of Fitness to Dive.

Introduction: Intrapulmonary pathology, such as bullae or blebs, can cause pulmonary barotrauma when diving. Many diving courses require chest X-rays (CXR) or high-resolution computed tomography (HRCT) to exclude asymptomatic healthy individuals with these lesions. The ability of routine CXRs and HRCT to assess fitness to dive has never been evaluated. Methods: Military divers who underwent yearly medical assessments at the Royal Netherlands Navy Diving Medical Center, including CXR at initial assessment, and who received a HRCT between January and June 2018, were included. The correlations of CXR and HRCT results with fitness to dive assessments were analyzed using Fisher's exact tests. Results: This study included 101 military divers. CXR identified bullae or blebs in seven divers, but HRCT found that these anomalies were not present in three subjects and were something else in four. CXR showed no anomalies in 94 subjects, but HRCT identified coincidental findings in 23 and bullae or blebs in seven. The differences between CXR and HRCT results were statistically significant (p = 0.023). Of the 34 subjects with anomalies on HRCT, 18 (53%) were disqualified for diving. Discussion: Routine CXR in asymptomatic military divers does not contribute to the identification of relevant pathology in fitness to dive assessments and has a high false negative rate (32%). HRCT is more diagnostic than CXR but yields unclear results, leading to disqualification for diving. Fitness to dive tests should exclude routine CXR; rather, HRCT should be performed only in subjects with clinical indications.

Detecting Pulmonary Oxygen Toxicity Using eNose Technology and Associations between Electronic Nose and Gas Chromatography-Mass Spectrometry Data.

Exposure to oxygen under increased atmospheric pressures can induce pulmonary oxygen toxicity (POT). Exhaled breath analysis using gas chromatography-mass spectrometry (GC-MS) has revealed that volatile organic compounds (VOCs) are associated with inflammation and lipoperoxidation after hyperbaric-hyperoxic exposure. Electronic nose (eNose) technology would be more suited for the detection of POT, since it is less time and resource consuming. However, it is unknown whether eNose technology can detect POT and whether eNose sensor data can be associated with VOCs of interest. In this randomized cross-over trial, the exhaled breath from divers who had made two dives of 1 h to 192.5 kPa (a depth of 9 m) with either 100% oxygen or compressed air was analyzed, at several time points, using GC-MS and eNose. We used a partial least square discriminant analysis, eNose discriminated oxygen and air dives at 30 min post dive with an area under the receiver operating characteristics curve of 79.9% (95%CI: 61.1-98.6; p = 0.003). A two-way orthogonal partial least square regression (O2PLS) model analysis revealed an R² of 0.50 between targeted VOCs obtained by GC-MS and eNose sensor data. The contribution of each sensor to the detection of targeted VOCs was also assessed using O2PLS. When all GC-MS fragments were included in the O2PLS model, this resulted in an R² of 0.08. Thus, eNose could detect POT 30 min post dive, and the correlation between targeted VOCs and eNose data could be assessed using O2PLS.

Pulmonary Oxygen Toxicity in Navy Divers: A Crossover Study Using Exhaled Breath Analysis After a One-Hour Air or Oxygen Dive at Nine Meters of Sea Water.

Introduction: Exposure to hyperbaric hyperoxic conditions can lead to pulmonary oxygen toxicity. Although a decrease in vital capacity has long been the gold standard, newer diagnostic modalities may be more accurate. In pulmonary medicine, much research has focussed on volatile organic compounds (VOCs) associated with inflammation in exhaled breath. In previous small studies after hyperbaric hyperoxic exposure several methyl alkanes were identified. This study aims to identify which VOCs mark the development of pulmonary oxygen toxicity. Methods: In this randomized crossover study, 12 divers of the Royal Netherlands Navy made two dives of one hour to 192.5 kPa (comparable to a depth of 9 msw) either with 100% oxygen or compressed air. At 30 min before the dive, and at 30 min and 1, 2, 3, and 4 h post-dive, exhaled breath was collected and followed by pulmonary function tests (PFT). Exhaled breath samples were analyzed using gas chromatography-mass spectrometry (GC-MS). After univariate tests and correlation of retention times, ion fragments could be identified using a standard reference database [National Institute of Standards and Technology (NIST)]. Using these fragments VOCs could be reconstructed, which were then tested longitudinally with analysis of variance. Results: After GC-MS analysis, seven relevant VOCs (generally methyl alkanes) were identified. Decane and decanal showed a significant increase after an oxygen dive (p = 0.020 and p = 0.013, respectively). The combined intensity of all VOCs showed a significant increase after oxygen diving (p = 0.040), which was at its peak (+35%) 3 h post-dive. Diffusion capacity of nitric oxide and alveolar membrane capacity showed a significant reduction after both dives, whereas no other differences in PFT were significant. Discussion: This study is the largest analysis of exhaled breath after in water oxygen dives to date and the first to longitudinally measure VOCs. The longitudinal setup showed an increase and subsequent decrease of exhaled components. The VOCs identified suggest that exposure to a one-hour dive with a partial pressure of oxygen of 192.5 kPa damages the phosphatidylcholine membrane in the alveoli, while the spirometry and diffusion capacity show little change. This suggests that exhaled breath analysis is a more accurate method to measure pulmonary oxygen toxicity.

Oxygen Toxicity and Special Operations Forces Diving: Hidden and Dangerous.

In Special Operations Forces (SOF) closed-circuit rebreathers with 100% oxygen are commonly utilized for covert diving operations. Exposure to high partial pressures of oxygen (PO2) could cause damage to the central nervous system (CNS) and pulmonary system. Longer exposure time and higher PO2 leads to faster development of more serious pathology. Exposure to a PO2 above 1.4 ATA can cause CNS toxicity, leading to a wide range of neurologic complaints including convulsions. Pulmonary oxygen toxicity develops over time when exposed to a PO2 above 0.5 ATA and can lead to inflammation and fibrosis of lung tissue. Oxygen can also be toxic for the ocular system and may have systemic effects on the inflammatory system. Moreover, some of the effects of oxygen toxicity are irreversible. This paper describes the pathophysiology, epidemiology, signs and symptoms, risk factors and prediction models of oxygen toxicity, and their limitations on SOF diving.

Oxygen, the lung and the diver: friends and foes?

Worldwide, the number of professional and sports divers is increasing. Most of them breathe diving gases with a raised partial pressure of oxygen (PO2 ). However, if the PO2 is between 50 and 300 kPa (375-2250 mmHg) (hyperoxia), pathological pulmonary changes can develop, known as pulmonary oxygen toxicity (POT). Although in its acute phase, POT is reversible, it can ultimately lead to non-reversible pathological changes. Therefore, it is important to monitor these divers to prevent them from sustaining irreversible lesions.This review summarises the pulmonary pathophysiological effects when breathing oxygen with a PO2 of 50-300 kPa (375-2250 mmHg). We describe the role and the limitations of lung function testing in monitoring the onset and development of POT, and discuss new techniques in respiratory medicine as potential markers in the early development of POT in divers.

Tympanic membrane bleeding complications during hyperbaric oxygen treatment in patients with or without antiplatelet and anticoagulant drug treatment.

INTRODUCTION: Middle ear barotrauma (MEBt) is a frequently occurring complication of hyperbaric oxygen treatment (HBOT). High-grade MEBt may involve tympanic membrane (TM) haemorrhaging. Although many patients undergoing HBOT use antiplatelet or anticoagulant drugs, it is unknown whether these drugs increase the risk of MEBt and particularly TM bleeding complications. METHODS: This multicentre, prospective cohort study investigates the prevalence of MEBt and TM bleeding during HBOT in patients using antiplatelet/anticoagulant drugs, compared with control patients not on such medications. MEBt was assessed by video otoscopy of the TM pre and post HBOT and scored according to the modified Teed score. Any complications from previous HBOT sessions were retrospectively documented. RESULTS: Of 73 patients receiving HBOT, 34 used antiplatelet/anticoagulant drugs. Mild MEBt (Teed score 1 or 2) occurred in 23 of these 34 patients and in 31 of the 39 controls. Teed score 3 MEBt occurred in only two of the control-group patients and none of the patients using antiplatelet/anticoagulant drugs. Two patients using anticoagulant drugs reported epistaxis during a previous HBOT session, epistaxis was not reported by any control patients. CONCLUSION: Low-grade MEBt is common during HBOT, however, high-grade barotrauma is rare with current chamber operating procedures. Patients using antiplatelet/anticoagulant drugs potentially may be prone to MEBt-associated haemorrhagic complications, but we did not observe any such increase in this cohort. Only mild epistaxis occurred in patients using anticoagulant drugs.

A retrospective cohort study of lidocaine in divers with neurological decompression illness.

Lidocaine is the most extensively studied substance for adjuvant therapy in neurological decompression illness (DCI), but results have been conflicting. In this retrospective cohort study, we compared 14 patients who received adjuvant intravenous lidocaine for neurological decompression sickness and cerebral arterial gas embolism between 2001 and 2011 against 21 patients who were treated between 1996 and 2001 and did not receive lidocaine. All patients were treated with hyperbaric oxygen (HBO2) therapy according to accepted guidelines. Groups were comparable for all investigated confounding factors, except that significantly more control patients had made an unsafe dive (62% vs. 14%, p = 0.007). Groups had comparable injury severity as measured by Dick and Massey score (lidocaine 2.7 +/- 1.7, control 2.0 +/- 1.6), an adapted version of the Dick and Massey score, and the Blatteau score. Number of HBO2 sessions given was comparable in both groups (lidocaine 2.7 +/- 2.3, control 2.0 +/- 1.0). There was neither a positive nor a negative effect of lidocaine on outcome (relative risk for objective neurological signs at follow-up in the lidocaine group was 1.8, 95% CI 0.2-16). This is the first retrospective cohort study of lidocaine in neurological DCI. Since our study is under-powered to draw definitive conclusions, a prospective multicenter study remains the only way to reliably determine the effect of lidocaine in neurological decompression illness.