Volume 50: The UHM Journal celebrates a milestone with the publication of this issue.

As the UHMS observes the distinguished anniversary of the publication of 50 volumes of the Undersea and Hyperbaric Medicine Journal, two of our past editors take a look at the evolution of our flagship publications.

Safety evaluation of carbon tetrafluoride as an inert hyperbaric breathing gas in Sprague-Dawley rats.

Carbon tetrafluoride (CF4) is an inert gas with higher molecular weight and lower water solubility than commonly used hyperbaric breathing gases. These inert gas properties decrease time required to decompress and avoid decompression sickness after deep dives. To assess CF4 toxicity, Sprague-Dawley rats were exposed to 8 atm absolute (ATA) air (10 males, 10 females) or 8 ATA 79% CF4/21% O2 (25 males, 25 females). Exposures were 30 min daily for 5 days. Rat behavior was normal throughout the testing period. There were no gross or microscopic pathology abnormalities following repeat dose exposure. Male body weight trends were similar between groups. Female body weight trends were 0.5 ± 0.8% day-1 for hyperbaric air exposure and - 0.2 ± 0.8% day-1 for hyperbaric CF4 exposure (P = 0.01) but remained within literature cited norms. Organ weights and hematologic indices remained within or near literature normal ranges. Clinical chemistry panels showed no signs of toxicity in renal or hepatic biomarkers. Polychromatic erythrocyte micronucleus frequency showed no chromosomal damage. Comet assay showed no DNA damage in lung tissue. Females exposed to CF4 had 2.5 times greater percent tail DNA in liver tissue than controls (P = 0.009). However this result remained within the normal range of local negative controls. A bacterial reverse mutation assay with exposure to 1 ATA 79% CF4/21% O2 for 72 h was nonmutagenic in four strains of Salmonella typhimurium and one strain of Escherichia coli. Overall, there was no evidence that CF4 caused organ toxicity or genetic toxicity.

Randomized controlled trial of 7, 28, vs 42 day stored red blood cell transfusion on oxygen delivery (VO2 max) and exercise duration.

BACKGROUND: Few studies have rigorously assessed the impact of red blood cell (RBC) transfusion on oxygen delivery. Several large trials demonstrated no clinical outcome differences between transfusion of shorter-storage vs prolonged-storage RBCs. These trials did not directly assess functional measures of oxygen delivery. Therefore, it is not clear if 42-day stored RBCs deliver oxygen as effectively as 7-day stored RBCs. STUDY DESIGN AND METHODS: Leukocyte-reduced RBCs were collected by apheresis in AS-3. Thirty subjects were randomized (1:1:1) to receive 2 units of autologous RBCs at either 7, 28, or 42 days following donation. VO2 max testing, using a standardized protocol to exhaustion, was performed 2 days before (Monday) and 2 days after (Friday) the transfusion visit (Wednesday). The primary endpoint was the percent increase in VO2 max between Monday and Friday. The secondary endpoint was the percent change in duration of exercise for the same time points. RESULTS: Hemoglobin levels decreased by 2.8 ± 1.4 g/dL after donation and increased by 2.1 ± 0.6 g/dL after transfusion. This change in hemoglobin was associated with expected decreases (then increases after transfusion) in VO2 max and exercise duration. No differences were observed between 7-day and 42-day RBC transfusion for percent increase in median [IQR] VO2 max (10.5 [0.2-17.3] vs 10.9 [5.7-16.8], P = .41) or for percent increase in exercise duration (5.4 [4.1-6.9] vs 4.9 [2.0-7.2], P = .91), respectively. Results were similar for 28-day RBCs and were consistent across the ITT and per-protocol analysis populations. CONCLUSION: These data indicate that 42-day, 28-day, and 7-day RBCs have similar ability to deliver oxygen.

Hyperbaric oxygen for intracranial abscess.

The term "intracranial abscess" (ICA) includes cerebral abscess, subdural empyema, and epidural empyema, which share many diagnostic and therapeutic similarities and, frequently, very similar etiologies. Infection may occur and spread from a contiguous infection such as sinusitis, otitis, mastoiditis, or dental infection; hematogenous seeding; or cranial trauma. In view of the high morbidity and mortality of ICA and the fact that hyperbaric oxygen therapy (HBO2) is relatively non-invasive and carries a low complication rate, the risk-benefit ratio favors adjunct use of HBO2 therapy in selected patients with intracranial abscess.

Hyperbaric oxygen for decompression sickness.

Decompression sickness (DCS, "bends") is caused by formation of bubbles in tissues and/or blood when the sum of dissolved gas pressures exceeds ambient pressure (supersaturation). This may occur when ambient pressure is reduced during any of the following: ascent from a dive; depressurization of a hyperbaric chamber; rapid ascent to altitude in an unpressurized aircraft or hypobaric chamber; loss of cabin pressure in an aircraft; and during space walks.

Ultrasound in decompression research: fundamentals, considerations, and future technologies.

It is widely accepted that bubbles are a necessary but insufficient condition for the development of decompression sickness. However, open questions remain regarding the precise formation and behavior of these bubbles after an ambient pressure reduction (decompression), primarily due to the inherent difficulty of directly observing this phenomenon in vivo. In decompression research, information about these bubbles after a decompression is gathered via means of ultrasound acquisitions. The ability to draw conclusions regarding decompression research using ultrasound is highly influenced by the variability of the methodologies and equipment utilized by different research groups. These differences play a significant role in the quality of the data and thus the interpretation of the results. The purpose of this review is to provide a technical overview of the use of ultrasound in decompression research, particularly Doppler and brightness (B)-mode ultrasound. Further, we will discuss the strengths and limitations of these technologies and how new advancements are improving our ability to understand bubble behavior post-decompression.

A fully automated method for late ventricular diastole frame selection in post-dive echocardiography without ECG gating.

Venous gas emboli (VGE) are often quantified as a marker of decompression stress on echocardiograms. Bubble-counting has been proposed as an easy to learn method, but remains time-consuming, rendering large dataset analysis impractical. Computer automation of VGE counting following this method has therefore been suggested as a means to eliminate rater bias and save time. A necessary step for this automation relies on the selection of a frame during late ventricular diastole (LVD) for each cardiac cycle of the recording. Since electrocardiograms (ECG) are not always recorded in field experiments, here we propose a fully automated method for LVD frame selection based on regional intensity minimization. The algorithm is tested on 20 previously acquired echocardiography recordings (from the original bubble-counting publication), half of which were acquired at rest (Rest) and the other half after leg flexions (Flex). From the 7,140 frames analyzed, sensitivity was found to be 0.913 [95% CI: 0.875-0.940] and specificity 0.997 [95% CI: 0.996-0.998]. The method's performance is also compared to that of random chance selection and found to perform significantly better (p≺0.0001). No trend in algorithm performance was found with respect to VGE counts, and no significant difference was found between Flex and Rest (p>0.05). In conclusion, full automation of LVD frame selection for the purpose of bubble counting in post-dive echocardiography has been established with excellent accuracy, although we caution that high quality acquisitions remain paramount in retaining high reliability.

Physiologic and biochemical rationale for treating COVID-19 patients with hyperbaric oxygen.

The SARS-Cov-2 (COVID-19) pandemic remains a major worldwide public health issue. Initially, improved supportive and anti-inflammatory intervention, often employing known drugs or technologies, provided measurable improvement in management. We have recently seen advances in specific therapeutic interventions and in vaccines. Nevertheless, it will be months before most of the world's population can be vaccinated to achieve herd immunity. In the interim, hyperbaric oxygen (HBO2) treatment offers several potentially beneficial therapeutic effects. Three small published series, one with a propensity-score-matched control group, have demonstrated safety and initial efficacy. Additional anecdotal reports are consistent with these publications. HBO2 delivers oxygen in extreme conditions of hypoxemia and tissue hypoxia, even in the presence of lung pathology. It provides anti-inflammatory and anti-proinflammatory effects likely to ameliorate the overexuberant immune response common to COVID-19. Unlike steroids, it exerts these effects without immune suppression. One study suggests HBO2 may reduce the hypercoagulability seen in COVID patients. Also, hyperbaric oxygen offers a likely successful intervention to address the oxygen debt expected to arise from a prolonged period of hypoxemia and tissue hypoxia. To date, 11 studies designed to investigate the impact of HBO2 on patients infected with SARS-Cov-2 have been posted on clinicaltrials.gov. This paper describes the promising physiologic and biochemical effects of hyperbaric oxygen in COVID-19 and potentially in other disorders with similar pathologic mechanisms.

Arterial blood gases in divers at surface after prolonged breath-hold.

PURPOSE: Adaptations during voluntary breath-hold diving have been increasingly investigated since these athletes are exposed to critical hypoxia during the ascent. However, only a limited amount of literature explored the pathophysiological mechanisms underlying this phenomenon. This is the first study to measure arterial blood gases immediately before the end of a breath-hold in real conditions. METHODS: Six well-trained breath-hold divers were enrolled for the experiment held at the "Y-40 THE DEEP JOY" pool (Montegrotto Terme, Padova, Italy). Before the experiment, an arterial cannula was inserted in the radial artery of the non-dominant limb. All divers performed: a breath-hold while moving at the surface using a sea-bob; a sled-assisted breath-hold dive to 42 m; and a breath-hold dive to 42 m with fins. Arterial blood samples were obtained in four conditions: one at rest before submersion and one at the end of each breath-hold. RESULTS: No diving-related complications were observed. The arterial partial pressure of oxygen (96.2 ± 7.0 mmHg at rest, mean ± SD) decreased, particularly after the sled-assisted dive (39.8 ± 8.7 mmHg), and especially after the dive with fins (31.6 ± 17.0 mmHg). The arterial partial pressure of CO2 varied somewhat but after each study was close to normal (38.2 ± 3.0 mmHg at rest; 31.4 ± 3.7 mmHg after the sled-assisted dive; 36.1 ± 5.3 after the dive with fins). CONCLUSION: We confirmed that the arterial partial pressure of oxygen reaches hazardously low values at the end of breath-hold, especially after the dive performed with voluntary effort. Critical hypoxia can occur in breath-hold divers even without symptoms.

Hyperbaric oxygen as a treatment for COVID-19 infection?

Recently the internet has been abuzz with new ideas to treat COVID-19, including hyperbaric oxygen (HBO2) therapy, undoubtedly driven by the fact that until recently there have been few therapeutic options for this highly contagious and often lethal infection. . . . Refractory hypoxemia is certainly treatable with hyperbaric oxygen due to the obvious effect of increasing inspired oxygen partial pressure (PO2), the major reason for using HBO2 for its established indications. However, the length of time during which patients can safely be administered HBO2 inside a chamber is limited, due to practical issues of confinement and isolation from other necessary medical interventions, but also because of oxygen toxicity.

Immersion pulmonary edema: drowning from the inside.

Immersion pulmonary (IPE, also known as swimming-induced pulmonary edema, SIPE) is a condition in which pulmonary edema develops rapidly during a dive or vigorous swim. Symptoms include dyspnea and hemoptysis. Physical exam reveals typical signs of bilateral pulmonary edema, which can be confirmed radiographically or with bedside ultrasound.

Hyperbaric treatment of air or gas embolism: current recommendations.

Gas can enter arteries (arterial gas embolism, AGE) due to alveolar-capillary disruption (caused by pulmonary over-pressurization, e.g. breath-hold ascent by divers) or veins (venous gas embolism, VGE) as a result of tissue bubble formation due to decompression (diving, altitude exposure) or during certain surgical procedures where capillary hydrostatic pressure at the incision site is subatmospheric. Both AGE and VGE can be caused by iatrogenic gas injection. AGE usually produces stroke-like manifestations, such as impaired consciousness, confusion, seizures and focal neurological deficits. Small amounts of VGE are often tolerated due to filtration by pulmonary capillaries; however VGE can cause pulmonary edema, cardiac "vapor lock" and AGE due to transpulmonary passage or right-to-left shunt through a patient foramen ovale. Intravascular gas can cause arterial obstruction or endothelial damage and secondary vasospasm and capillary leak. Vascular gas is frequently not visible with radiographic imaging, which should not be used to exclude the diagnosis of AGE. Isolated VGE usually requires no treatment; AGE treatment is similar to decompression sickness (DCS), with first aid oxygen then hyperbaric oxygen. Although cerebral AGE (CAGE) often causes intracranial hypertension, animal studies have failed to demonstrate a benefit of induced hypocapnia. An evidence based review of adjunctive therapies is presented.

Hyperbaric treatment for decompression sickness: current recommendations.

Decompression sickness (DCS, "bends") is caused by formation of bubbles in tissues and/or blood when the sum of dissolved gas pressures exceeds ambient pressure (supersaturation). This may occur when ambient pressure is reduced during any of the following: ascent from a dive; depressurization of a hyperbaric chamber; rapid ascent to altitude in an unpressurised aircraft or hypobaric chamber; loss of cabin pressure in an aircraft [2] and during space walks.

Using the Electronic Medical Record to Improve Preoperative Identification of Patients at Risk for Obstructive Sleep Apnea.

PURPOSE: Obstructive sleep apnea (OSA) is a breathing disorder found in surgical patients and associated with complications in the postoperative period. The implementation of a preoperative universal screening process using the STOP-BANG questionnaire to identify patients at high risk for OSA provides opportunities for improved management. DESIGN: A pre-post design was used to evaluate screening compliance rates. METHODS: This initiative included staff education, which included the process for evaluating and documenting STOP-BANG scores. The data were collected via a chart review of the electronic medical record (EMR). FINDINGS: The rate of screening for OSA doubled after implementation of this initiative, and compliance with STOP-BANG questionnaire screening was 66.1%. High-risk designation in the EMR was 73.0%. Nearly half of the patients screened were found to be at high risk for OSA. CONCLUSIONS: Implementation of a universal screening initiative for patients and design for the EMR improves compliance with screening and identification of patients at high risk for OSA.

Swimming-Induced Pulmonary Edema: Pathophysiology and Risk Reduction With Sildenafil.

BACKGROUND: Swimming-induced pulmonary edema (SIPE) occurs during swimming or scuba diving, often in young individuals with no predisposing conditions, and its pathophysiology is poorly understood. This study tested the hypothesis that pulmonary artery and pulmonary artery wedge pressures are higher in SIPE-susceptible individuals during submerged exercise than in the general population and are reduced by sildenafil. METHODS AND RESULTS: Ten study subjects with a history of SIPE (mean age, 41.6 years) and 20 control subjects (mean age, 36.2 years) were instrumented with radial artery and pulmonary artery catheters and performed moderate cycle ergometer exercise for 6 to 7 minutes while submersed in 20°C water. SIPE-susceptible subjects repeated the exercise 150 minutes after oral administration of 50 mg sildenafil. Work rate and mean arterial pressure during exercise were similar in controls and SIPE-susceptible subjects. Average o2 and cardiac output in controls and SIPE-susceptible subjects were: o2 2.42 L·min(-1) versus 1.95 L·min(-1), P=0.2; and cardiac output 17.9 L·min(-1) versus 13.8 L·min(-1), P=0.01. Accounting for differences in cardiac output between groups, mean pulmonary artery pressure at cardiac output=13.8 L·min(-1) was 22.5 mm Hg in controls versus 34.0 mm Hg in SIPE-susceptible subjects (P=0.004), and the corresponding pulmonary artery wedge pressure was 11.0 mm Hg versus 18.8 mm Hg (P=0.028). After sildenafil, there were no statistically significant differences in mean pulmonary artery pressure or pulmonary artery wedge pressure between SIPE-susceptible subjects and controls. CONCLUSIONS: These observations confirm that SIPE is a form of hemodynamic pulmonary edema. The reduction in pulmonary vascular pressures after sildenafil with no adverse effect on exercise hemodynamics suggests that it may be useful in SIPE prevention. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00815646.

A randomized controlled pilot study of VO2 max testing: a potential model for measuring relative in vivo efficacy of different red blood cell products.

BACKGROUND: Randomized trials, for example, RECESS, comparing "young" (median, 7-day) versus "middle-aged" (median, 28-day) red blood cells (RBCs), showed no difference in outcome. These data are important; however, they do not inform us about the safety and effectiveness of the oldest RBCs, which some patients receive. It may not be feasible to conduct a clinical trial randomizing patients to receive the oldest blood. Therefore, we propose strenuous exercise (VO2 max testing) as a model to study the relative efficacy to increase oxygen delivery to tissue of different RBC products, for example, extremes of storage duration. STUDY DESIGN AND METHODS: In this pilot study, eight healthy subjects had 2 units of leukoreduced RBCs collected by apheresis in AS-3 using standard methods. Subjects were randomized to receive both (2) units of their autologous RBCs at either 7 or 42 days after blood collection. VO2 max testing on a cycle ergometer was performed 2 days before (Monday) and 2 days after (Friday) the transfusion visit (Wednesday). This design avoids confounding effects on intravascular volume from the 2-unit blood transfusion. The primary outcome was the difference in VO2 max between Friday and Monday (delta VO2 max). RESULTS: VO2 max increased more in the 7-day RBC arm (8.7 ± 6.9% vs. 1.9 ± 6.5%, p = 0.202 for comparison between arms). Exercise duration (seconds) increased in the 7-day RBC arm (8.4 ± 1.7%) but actually decreased in the 42-day arm (-2.6 ± 3.6%, p = 0.002). CONCLUSIONS: This pilot study suggests that VO2 max testing has potential as a rigorous and quantitative in vivo functional assay of RBC function. Our preliminary results suggest that 42-day RBCs are inferior to 7-day RBCs at delivering oxygen to tissues.

Marriage and mortality after noncardiac surgery.

BACKGROUND: Marriage is linked to substantial societal and economic benefits, and it has been associated with improved outcomes following acute illness. However, it is not known if being married confers benefit to patients undergoing noncardiac surgical procedures. MATERIALS AND METHODS: Patients undergoing any noncardiac surgical procedure were included over a period of 19 months. All-cause mortality at 2 years was determined by linking patient records to the National Death Index. Risk adjustment was performed using Cox modeling and the Cleveland Clinic risk stratification index. RESULTS: Of the 11,588 patients included, 7830 (68.0%) were married at the time of surgery. There was a significant interaction between sex and marital status (P = 0.03), so the remainder of the analysis was performed separately by sex. Among men, not being married was associated with significantly worse survival (hazard ratio [HR]: 1.31, 95% confidence interval [CI]: 1.06, 1.63), whereas among women, there was no significant association between marital status and survival (HR: 0.94, 95% CI: 0.77, 1.15). Furthermore, divorced men (HR: 1.76, 95% CI: 1.25, 2.51) and never married men (HR: 1.53, 95% CI: 1.14, 2.05) had significantly worse survival than married men, whereas there was no significant difference between widowed men and married men, nor when comparing widowed, divorced, or never married women to married women. CONCLUSIONS: Among a diverse group of surgical patients, being married at the time of surgery is associated with significantly improved survival only among men. Focused efforts to improve social support for unmarried male patients may improve outcomes.