Selecting optimal air diving gradient factors for Belgian military divers: more conservative settings are not necessarily safer.

Introduction: In 2018, the Belgian Defence introduced a commercial off-the-shelf dive computer (Shearwater Perdix™) for use by its military divers. There were operational constraints when using its default gradient factors (GF). We aimed to provide guidelines for optimal GF selection. Methods: The Defence and Civil Institute of Environmental Medicine (DCIEM) dive tables and the United States Navy (USN) air decompression tables are considered acceptably safe by the Belgian Navy Diving Unit. The decompression model used in the Shearwater Perdix (Bühlmann ZH-L16C algorithm with GF) was programmed in Python. Using a sequential search of the parameter space, the GF settings were optimised to produce decompression schedules as close as possible to those prescribed by the USN and DCIEM tables. Results: All reference profiles are approached when GFLO is kept equal to 100 and only GFHI is reduced to a minimum of 75 to prolong shallower stop times. Using the Perdix default settings (GFLO = 30 and GFHI = 70) yields deeper initial stops, leading to increased supersaturation of the 'slower' tissues, which potentially leads to an increased DCS risk. However, Perdix software does not currently allow for the selection of our calculated optimal settings (by convention GFLO < GFHI). A sub-optimal solution would be a symmetrical GF setting between 75/75 and 95/95. Conclusions: For non-repetitive air dives, the optimal GF setting is GFLO 100, with only the GFHI parameter lowered to increase safety. No evidence was found that using the default GF setting (30/70) would lead to a safer decompression for air dives as deep as 60 metres of seawater; rather the opposite. Belgian Navy divers have been advised against using the default GF settings of the Shearwater Perdix dive computer and instead adopt symmetrical GF settings which is currently the optimal achievable approach considering the software constraints.

Oxidative Stress Response Kinetics after 60 Minutes at Different (1.4 ATA and 2.5 ATA) Hyperbaric Hyperoxia Exposures.

Hyperbaric oxygen therapy (HBOT) is a therapeutical approach based on exposure to pure oxygen in an augmented atmospheric pressure. Although it has been used for years, the exact kinetics of the reactive oxygen species (ROS) between different pressures of hyperbaric oxygen exposure are still not clearly evidenced. In this study, the metabolic responses of hyperbaric hyperoxia exposures for 1 h at 1.4 and 2.5 ATA were investigated. Fourteen healthy non-smoking subjects (2 females and 12 males, age: 37.3 ± 12.7 years old (mean ± SD), height: 176.3 ± 9.9 cm, and weight: 75.8 ± 17.7 kg) volunteered for this study. Blood samples were taken before and at 30 min, 2 h, 24 h, and 48 h after a 1 h hyperbaric hyperoxic exposure. The level of oxidation was evaluated by the rate of ROS production, nitric oxide metabolites (NOx), and the levels of isoprostane. Antioxidant reactions were assessed through measuring superoxide dismutase (SOD), catalase (CAT), cysteinylglycine, and glutathione (GSH). The inflammatory response was measured using interleukine-6, neopterin, and creatinine. A short (60 min) period of mild (1.4 ATA) and high (2.5 ATA) hyperbaric hyperoxia leads to a similar significant increase in the production of ROS and antioxidant reactions. Immunomodulation and inflammatory responses, on the contrary, respond proportionally to the hyperbaric oxygen dose. Further research is warranted on the dose and the inter-dose recovery time to optimize the potential therapeutic benefits of this promising intervention.

Varying Oxygen Partial Pressure Elicits Blood-Borne Microparticles Expressing Different Cell-Specific Proteins-Toward a Targeted Use of Oxygen?

Oxygen is a powerful trigger for cellular reactions, but there are few comparative investigations assessing the effects over a large range of partial pressures. We investigated a metabolic response to single exposures to either normobaric (10%, 15%, 30%, 100%) or hyperbaric (1.4 ATA, 2.5 ATA) oxygen. Forty-eight healthy subjects (32 males/16 females; age: 43.7 ± 13.4 years, height: 172.7 ± 10.07 cm; weight 68.4 ± 15.7 kg) were randomly assigned, and blood samples were taken before and 2 h after each exposure. Microparticles (MPs) expressing proteins specific to different cells were analyzed, including platelets (CD41), neutrophils (CD66b), endothelial cells (CD146), and microglia (TMEM). Phalloidin binding and thrombospondin-1 (TSP), which are related to neutrophil and platelet activation, respectively, were also analyzed. The responses were found to be different and sometimes opposite. Significant elevations were identified for MPs expressing CD41, CD66b, TMEM, and phalloidin binding in all conditions but for 1.4 ATA, which elicited significant decreases. Few changes were found for CD146 and TSP. Regarding OPB, further investigation is needed to fully understand the future applications of such findings.

Hypoxic and Hyperoxic Breathing as a Complement to Low-Intensity Physical Exercise Programs: A Proof-of-Principle Study.

Inflammation is an adaptive response to both external and internal stimuli including infection, trauma, surgery, ischemia-reperfusion, or malignancy. A number of studies indicate that physical activity is an effective means of reducing acute systemic and low-level inflammation occurring in different pathological conditions and in the recovery phase after disease. As a proof-of-principle, we hypothesized that low-intensity workout performed under modified oxygen supply would elicit a "metabolic exercise" inducing a hormetic response, increasing the metabolic load and oxidative stress with the same overall effect expected after a higher intensity or charge exercise. Herein, we report the effect of a 5-week low-intensity, non-training, exercise program in a group of young healthy subjects in combination with the exposure to hyperoxia (30% and 100% pO2, respectively) or light hypoxia (15% pO2) during workout sessions on several inflammation and oxidative stress parameters, namely hemoglobin (Hb), redox state, nitric oxide metabolite (NOx), inducible nitric oxide synthase (iNOS), inflammatory cytokine expression (TNF-α, interleukin (IL)-6, IL-10), and renal functional biomarkers (creatinine, neopterin, and urates). We confirmed our previous reports demonstrating that intermittent hyperoxia induces the normobaric oxygen paradox (NOP), a response overlapping the exposure to hypoxia. Our data also suggest that the administration of modified air composition is an expedient complement to a light physical exercise program to achieve a significant modulation of inflammatory and immune parameters, including cytokines expression, iNOS activity, and oxidative stress parameters. This strategy can be of pivotal interest in all those conditions characterized by the inability to achieve a sufficient workload intensity, such as severe cardiovascular alterations and articular injuries failing to effectively gain a significant improvement of physical capacity.

Preconditioning to Reduce Decompression Stress in Scuba Divers.

BACKGROUND: Using ultrasound imaging, vascular gas emboli (VGE) are observed after asymptomatic scuba dives and are considered a key element in the potential development of decompression sickness (DCS). Diving is also accompanied with vascular dysfunction, as measured by flow-mediated dilation (FMD). Previous studies showed significant intersubject variability to VGE for the same diving exposure and demonstrated that VGE can be reduced with even a single pre-dive intervention. Several preconditioning methods have been reported recently, seemingly acting either on VGE quantity or on endothelial inflammatory markers. METHODS: Nine male divers who consistently showed VGE postdive performed a standardized deep pool dive (33 m/108 ft, 20 min in 33°C water temperature) to investigate the effect of three different preconditioning interventions: heat exposure (a 30-min session of dry infrared sauna), whole-body vibration (a 30-min session on a vibration mattress), and dark chocolate ingestion (30 g of chocolate containing 86% cocoa). Dives were made one day per week and interventions were administered in a randomized order. RESULTS: These interventions were shown to selectively reduce VGE, FMD, or both compared to control dives. Vibration had an effect on VGE (39.54%, SEM 16.3%) but not on FMD postdive. Sauna had effects on both parameters (VGE: 26.64%, SEM 10.4%; FMD: 102.7%, SEM 2.1%), whereas chocolate only improved FMD (102.5%, SEM 1.7%). DISCUSSION: This experiment, which had the same subjects perform all control and preconditioning dives in wet but completely standardized diving conditions, demonstrates that endothelial dysfunction appears to not be solely related to VGE.Germonpré P, Balestra C. Preconditioning to reduce decompression stress in scuba divers. Aerosp Med Hum Perform. 2017; 88(2):114-120.

Poorly designed research does not help clarify the role of hyperbaric oxygen in the treatment of chronic diabetic foot ulcers.

Diabetic foot ulcers (DFUs) are one of the most common indications for hyperbaric oxygen treatment (HBOT). The role of HBOT in DFUs is often debated. Recent evidence based guidelines, while recommending its use, urge further studies to identify the patient subgroups most likely to benefit from HBOT. A recent study in Diabetes Care aimed to assess the efficacy of HBOT in reducing the need for major amputation and improving wound healing in patients with chronic DFUs. In this study, patients with Wagner grade 2-4 diabetic foot lesions were randomly assigned to have HBOT (30 sessions/90 min/244 kPa) or sham treatment (30 sessions/90 min/air/125 kPa). Six weeks after the completion of treatment (12 weeks after randomization) neither the fulfillment of major amputation criteria (11/49 vs. 13/54, odds ratio 0.91 [95% CI 0.37, 2.28], P = 0.846) nor wound-healing rates (20% vs. 22%, 0.90 [0.35, 2.31], P = 0.823) significantly differed between groups. The authors concluded that HBOT does not offer any additional advantage over comprehensive wound care. Since this paper was published in Diabetes Care, one of the most prestigious diabetes journals, it is likely it will have a major impact on the clinical practice of many physicians dealing with diabetic foot problems. Although from a methodological standpoint the conduct of the study (prospective, double-blind, randomized, controlled) seems to be close to ideal, several significant flaws render the conclusions weak. Firstly, there were some problems with the assessment of the primary outcome of "meeting the criteria for amputation". In their published protocol paper, the trial lists indicated that "At the end of the 6-week follow-up phase……, the patient is sent to the participating vascular surgeon for an amputation evaluation". However, in the published report in Diabetes Care, it is evident that patients were not assessed in a face-to-face consultation, but rather by the remote examination of wound photographs and clinical data "Participant clinical data together with digital photographs of the study wound progress were presented to the vascular surgeon". This departure from the original intent undermines the primary outcome of the study significantly. Fedorko et al claim this method of assessment has been validated, but neither of their supporting citations appear to substantiate this claim. Wirthlin et al assessed the level of agreement about a collection of wounds between surgeons who were present at the bedside and a remote group who assessed the wounds using a short clinical account and digital photography. There was reasonable agreement between onsite and remote, although the specificity for particular signs ranged from just 27% (erythema) to 100% (ischaemia). Importantly, only a subset of eight of the 24 included patients had non-healing wounds and the proportion of those that were associated with diabetes mellitus is unknown. Further, the need for amputation was not among the management decisions examined. Wirthlin et al concluded "a prospective trial of remote wound management …. is needed to further validate this technology." The authors of the second supposedly supporting citation were mainly interested in the assessment of pressure ulcers by digital photography using the Photographic Wound Assessment Tool (PWAT) compared to the Pressure Sore Status Tool (PSST). Of the 81 included lower leg ulcers, it is not clear how many were associated with diabetes mellitus. Indications for amputation were not considered. The authors concluded "The PWAT may be valuable when a bedside assessment cannot be made. However, the size of circular wounds, wound depth, undermining/tunneling, and odor cannot be assessed using photographs." In the Fedorko paper, the decision that there was an indication for amputation was made by the remote vascular surgeon by meeting any of the following criteria: "persistent deep infection involving bone and tendons (antibiotics required, hospitalization required, pathogen involved); ongoing risk of severe systemic infection related to the wound; inability to bear weight on the affected limb; or pain causing significant disability". We are particularly concerned that the criteria, "persistent deep infection involving bone and tendons", is subjective. Recent studies have demonstrated that diabetic foot osteomyelitis may not necessarily require amputation and some cases may be cured with antibiotic therapy alone. It is interesting to note that despite the high numbers of participants assessed as fitting the requirements for amputation (23% overall), no patient actually had a major amputation. The amputation outcome is inappropriately assessed, done at the wrong time, and the study is grossly underpowered to find any difference in the rate of true major amputation. Finally, whether the surgeon performed a baseline assessment of amputation prior to the randomised intervention is unknown. A comparison between the pre- and post-study estimates of amputation rates could have contributed to the interpretation of the results. Secondly, the authors fail to provide a clear comparison of peripheral arterial disease (PAD) between the groups. Although patients were randomized and those who were possible candidates for major vessel revascularization were excluded from the study, microvascular status was not assessed. No transcutaneous oxygen measurements were made on any of the patients. Given that, firstly, the risk of microvascular vessel compromise increases with diabetes duration, and secondly, transcutaneous oxygen measurements correlate with the possibility of good response to HBOT, it is possible that clinically significant differences between groups were undetected. As an example, patients in the HBOT group had a markedly longer mean duration of diabetes (19.1 vs. 12.4 years) and would be likely to have more severe microvascular disease. Thirdly, the follow-up period of six weeks after completion of treatment is very short. The study to which the authors refer to justify this follow-up period enrolled only patients with ulcers of Wagner grade 1 or 2 and specifically excluded patients with infection or ischaemia. These are not representative of the patient population treated with HBOT. The outcomes in patients with DFUs treated with HBOT should be assessed over a longer period. One such randomized controlled study demonstrated that patients receiving HBOT had significantly higher healing rates than placebo at one-year follow-up (25/48 (52%) versus 12/42 (29%); P 〈 0.03), but not at 12 weeks. Fourthly, the authors also failed to describe the experience of the vascular surgeon who adjudicated the wounds for amputation; how many years he was involved in the management of diabetic foot wounds or how specialized his practice was with these patients. Objective and universally recognized indications for amputation are yet to be established. Therefore, a multidisciplinary decision-making approach, rather than a single physician's decision, would have increased the credibility of the conclusion the authors reached. Notably, all previous studies of HBOT in this area have used actual amputation rates in order to have a clear clinical endpoint. Careful patient selection is paramount for the cost-effective use of HBOT as an adjunct to normal wound care in diabetic wounds. As it is possible to identify wounds that have no potential to heal despite HBOT, all studies should incorporate transcutaneous oxygen measurements in their baseline evaluation. As the wounds in this study tended to be small (6.1cm² and 5.8cm² on average) and had persisted for (on average) one year despite state-of-the-art previous wound care, it is likely that at least some of these would not meet the predictive minimal criteria for healing potential with HBOT. The findings of this study do indeed show that the indiscriminate treatment of all diabetic wounds with HBOT is probably not (cost-) effective; however, the study conclusion that "HBO has no benefit in the treatment of chronic diabetic foot wounds" is erroneous.

Hyperbaric oxygen therapy for acute noise-induced hearing loss: evaluation of different treatment regimens.

INTRODUCTION: Impulse noise from firearms is a common cause of acute acoustic trauma (AAT), which is characterized by high-frequency hearing loss and tinnitus. Various treatment modalities have been proposed, some combining medical treatment with hyperbaric oxygen (HBOT) in various ways. We have reviewed the therapeutic effect of primary protocols, with or without HBOT, used in our hospital. METHODS: Sixty-eight soldiers for all of whom pre-AAT audiometry tests were available, were treated with one of three different regimens. Group 1 received oral medication only. Group 2 received HBOT twice a day for 3 days then once a day (7 days), combined with intravenous medication (5 days) followed by oral treatment. Group 3 received HBOT once a day and oral medication for 10 days. Medical treatment consisted of methylprednisolone and piracetam in all groups. Control audiometry was performed after 10 days. Average Hearing Gain (AHG) and Average Residual Hearing Loss (ARHL) were calculated. RESULTS: The mean AHG in Group 1 was +5.58 ± 3.58 dB (mean ± SD); in Group 2 it was +20.62 ± 17.68 dB; and in Group 3 +17.0 ± 14.0 dB (P = 0.001, Kruskal-Wallis test). The mean ARHL without HBOT was -14.7 ± 8.27 dB (Group 1), and respectively -2.36 ± 10.69 dB (Group 2) and -5.0 ± 8.0 dB (Group 3) in the HBOT groups (P = 0.001, Kruskal-Wallis test). CONCLUSION: These results indicate a significant benefit for the combination of HBOT and medical therapy over medical treatment alone. Which of the two HBOT regimens is the more effective, remains to be determined.

Predive sauna and venous gas bubbles upon decompression from 400 kPa.

INTRODUCTION: This study investigated the influence of a far infrared-ray dry sauna-induced heat exposure before a simulated dive on bubble formation, and examined the concomitant adjustments in hemodynamic parameters. METHODS: There were 16 divers who were compressed in a hyperbaric chamber to 400 kPa (30 msw) for 25 min and decompressed at 100 kPa x min(-1) with a 4-min stop at 130 kPa. Each diver performed two dives 5 d apart, one with and one without a predive sauna session for 30 min at 65 degrees C ending 1 h prior to the dive. Circulating venous bubbles were detected with a precordial Doppler 20, 40, and 60 min after surfacing, at rest, and after flexions. Brachial artery flow mediated dilation (FMD), blood pressure, and bodyweight measurements were taken before and after the sauna session along with blood samples for analysis of plasma volume (PV), protein concentrations, plasma osmolality, and plasma HSP70. RESULTS: A single session of sauna ending 1 h prior to a simulated dive significantly reduced bubble formation [-27.2% (at rest) to 35.4% (after flexions)]. The sauna session led to an extracellular dehydration, resulting in hypovolemia (-2.7% PV) and -0.6% bodyweight loss. A significant rise of FMD and a reduction in systolic blood pressure and pulse pressure were observed. Plasma HSP70 significantly increased 2 h after sauna completion. CONCLUSION: A single predive sauna session significantly decreases circulating bubbles after a chamber dive. This may reduce the risk of decompression sickness. Sweat dehydration, HSP, and the NO pathway could be involved in this protective effect.

Influences of atmospheric pressure and temperature on intraocular pressure.

PURPOSE: To determine whether the atmospheric pressure (ATM) change experienced during diving can induce changes in the intraocular pressure (IOP) of eyes in a normal population. METHODS: The IOP of 27 healthy volunteers (ages, 23.8 +/- 4.9 years; range, 18-44) was measured with a Perkins applanation tonometer by two independent investigators who were masked to the previous measurements. Measurements were taken at baseline (normal ATM, 1 Bar and 24 degrees C), at 28 degrees C and 24 degrees C after the ATM was increased to 2 Bar in a hyperbaric chamber, at baseline again, and finally at the normal ATM of 1 Bar but a temperature of 28 degrees C. Multivariate regression analysis was used to evaluate the RESULTS: results. The mean IOP decreased significantly from 11.8 mm Hg in the right eye (RE) and 11.7 mm Hg in the left eye (LE) at 1 Bar to 10.7 mm Hg (RE) and 10.3 mm Hg (LE) at 2 Bar (P = 0.024, RE; P = 0.0006, LE). The IOP decrease remained constant during the ATM increase period (40 minutes) and was independent of the temperature change. The temperature increase alone did not significantly influence the IOP. CONCLUSIONS: An increase of the ATM to 2 Bar (equal to conditions experienced during underwater diving at 10 meters) modestly but significantly decreased the IOP independently of the temperature change. During the period of increased ATM (60 minutes), the IOP decrease remained stable and was independent of blood pressure change or corneal thickness.

Serum erythropoietin levels in healthy humans after a short period of normobaric and hyperbaric oxygen breathing: the "normobaric oxygen paradox".

Renal (peritubular) tissue hypoxia is a well-known physiological trigger for erythropoietin (EPO) production. We investigated the effect of rebound relative hypoxia after hyperoxia obtained under normo- and hyperbaric oxygen breathing conditions. A group of 16 healthy volunteers were investigated before and after a period of breathing 100% normobaric oxygen for 2 h and a period of breathing 100% oxygen at 2.5 ATA for 90 min (hyperbaric oxygen). Serum EPO concentration was measured using a radioimmunoassay at various time points during 24-36 h. A 60% increase (P < 0.001) in serum EPO was observed 36 h after normobaric oxygen. In contrast, a 53% decrease in serum EPO was observed at 24 h after hyperbaric oxygen. Those changes were not related to the circadian rhythm of serum EPO of the subjects. These results indicate that a sudden and sustained decrease in tissue oxygen tension, even above hypoxia thresholds (e.g., after a period of normobaric oxygen breathing), may act as a trigger for EPO serum level. This EPO trigger, the "normobaric oxygen paradox," does not appear to be present after hyperbaric oxygen breathing.