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.

Hyperbaric medicine simulation education curriculum: CNS toxicity during Treatment Table 6 and intubated ICU patient with mucous plugging.

INTRODUCTION/BACKGROUND: The incidence of complications and number of critically ill patients in hyperbaric medicine is relatively low [1]. This poses a challenge to those tasked with educating trainees as well as maintaining the skills of staff. Hyperbaric medicine fellows may not be exposed to critical patient scenarios or complications of hyperbaric medicine during a one-year fellowship. Additional staff may be unfamiliar with these situations as well. The purpose of hyperbaric simulation curriculum is to train health care providers for rare situations. To our knowledge, this hyperbaric simulation curriculum is the first published use of simulation education in the specialty of undersea and hyperbaric medicine. MATERIALS AND METHODS: Two simulation cases have been developed that involve a patient with oxygen toxicity during hyperbaric treatment as well as an ICU patient with mucous plugging. RESULTS: Medical training simulations are an effective method of teaching content and training multiple roles in Undersea and Hyperbaric Medicine. SUMMARY/CONCLUSIONS: A hyperbaric simulation curriculum is an achievable educational initiative that is able to train multiple team members simultaneously in situations that they may not encounter on a regular basis. We believe that this could be easily exported to otherinstitutions for further education.

Oxygen exposures at NASA's Neutral Buoyancy Lab: a 20-year experience.

Astronauts training for extravehicular activity (EVA) operations can spend many hours submerged underwater in a pressurized suit, called an extravehicular mobility unit (EMU), exposed to pressures exceeding 2 atmospheres absolute (ATA). To minimize the risk of decompression sickness (DCS) a 46% nitrox mixture is used. This limits the nitrogen partial pressure, decreasing the risk of DCS. The trade-off with using a 46% nitrox mixture is the increased potential for oxygen toxicity, which can lead to severe neurologic symptoms including seizures. Suited runs, which typically expose astronauts of 0.9-1.1 ATA for longer than six hours, routinely exceed the recommendation for central nervous system oxygen toxicity limits (CNSOTL) published by the National Oceanic and Atmospheric Administration (NOAA). Fortunately, in over 50,000 hours of suited training dives spanning 20 years of EVA training operations at NASA's Neutral Buoyancy Laboratory (NBL) there has never been an occurrence of oxygen toxicity. This lends support to anecdotal sentiment among certain members of the hyperbaric community that the NOAA CNSOTL recommendations might be overly conservative, at least for the oxygen pressure and time regime in which NBL operates. The NOAA CNSOTL recommendations are the result of expert consensus with a focus on safety and do not necessarily reflect rigorous experimental evidence. The data from the NBL suited dive operations provide a foundation of evidence that can help inform the expert discussion on dive-related neurologic oxygen toxicity performance and overnight recovery in young, healthy males.

Residual oxygen time model for oxygen partial pressure near 130 kPa (1.3 atm).

A two-part residual oxygen time model predicts the probability of detectible pulmonary oxygen toxicity P(P[O2tox]) after dives with oxygen partial pressure (PO2) approximately 130 kPa, and provides a tool to plan dive series with selected risk of P[O2tox]. Data suggest that pulmonary oxygen injury at this PO2 is additive between dives. Recovery begins after a delay and continues during any following dive. A logistic relation expresses P(P[O2tox]) as a function of dive duration (T(dur)) [hours]: P(P[O2tox]) = 100/[1+exp (3.586-0.49 x T(dur))] This expression maps T(dur) to P(P[O2tox]) or, in the linear mid-portion of the curve, P(P[O2tox]) usefully to T(dur). For multiple dives or during recovery, it maps to an equivalent dive duration, T(eq). T(eq) was found after second dives of duration T(dur 2). Residual time from the first dive t(r) = T(eq) - T(dur2). With known t(r), t and T(dur) a recovery model was fitted. t(r) = T(dur) x exp [-k x((t-5)/T(dur)2], where t = t - 5 hours, k = 0.149 for resting, and 0.047 for exercising divers, and t represents time after surfacing. The fits were assessed for 1,352 man-dives. Standard deviations of the residuals were 8.5% and 18.3% probability for resting or exercise dives, respectively.

[The change of NOS in pulmonary oxygen toxicity induced by different oxygen pressure].

OBJECTIVE: Long time exhaled oxygen will induced oxygen toxicity. Some studies had found that different pathology may exised in normobaric and hyperbaric pulmonary oxygen toxicity, and nitric oxide synthase (NOS) may play a role. In this study, we discussed the change of NOS in normobaric and hyperbaric pulmonary oxygen toxicity. METHODS: Sixty male SD rats were randomly divided into 6 groups (n = 10), exposed to 1 ATA (atmosphere absolute), 1.5 ATA, 2 ATA, 2.5 ATA and 3 ATA, 100% oxygen for 56, 20, 10, 8, 6 hours respectively. Rats were exposed to air as control. After exposure, the protein in bronchoalveolar lavage fluid (BALF), the wet/dry weight of lung and the expression of eNOS, nNOS in lung were defined. RESULTS: As compared to air group, the protein in BALF, the wet/dry of lung were significantly elevated in 1.0 ATA group, while these changes were not so obviously in the other groups, and these changes in hyperbaric oxygen group (approximately 1.0 ATA) were significantly decreased as compared with nonnrmobaric oxygen group (1.0 ATA). The expression of nNOS were not changed in normobaric and hyperbaric pulmonary oxygen toxicity, while the expression of eNOS was significantly decreased in 2 ATA group, and significantly elevated in 2.5 ATA and 3 ATA group. CONCLUSION: The expression of eNOS can change when exposed to different pressures of oxygen.

Brief screening test of ventilatory sensitivity to CO2 cannot replace the mandatory test for susceptibility to CNS oxygen toxicity.

Central nervous system oxygen toxicity is a major risk in closed-circuit diving, and the risk increases with elevation of the inspired carbon dioxide (CO2). Mandatory tests for CO2 retention and detection are common practice at the Israel Naval Medical Institute, for the instruction and selection of combat divers at an advanced stage in their training. Read test is a simpler test of the ventilatory response to CO2. Positive correlation between parameters from Read and mandatory tests, enable conducting the test at an earlier stage in diving candidates. In the mandatory test, divers (n = 45) breathing various levels of CO2 in oxygen, and tested for the detection and retention of CO2 reported their sensations. In the Read test, we recorded end-tidal CO2 and ventilation in subjects as they rebreathed from rubber bag. The slope of ventilation was calculated as a function of end-tidal CO2. There was low correlation between any of the parameters from our test and the Read test. There was low insignificant correlation between any parameter from the Read test and detection or retention of CO2. We cannot use the Read test as a test for CO2 retention or detection at an earlier stage in diving candidates.

Side effects of hyperbaric oxygen therapy.

Several side effects and complications from hyperbaric oxygen (HBO2) therapy have been described, with varying degrees of seriousness. By far, the two most frequent and benign side effects comprise middle ear barotrauma, which has been noted in up to 2% of treated patients, and can be prevented or minimized by teaching autoinflation techniques, or by inserting tympanostomy tubes. Another frequent complaint is claustrophobia, both during multiplace and monoplace chamber compression, requiring reassurance, coaching and, at times, sedation. Other more rare, but more severe side effects derive from oxygen (O2) toxicity, from the multiple exposures required for chronic treatments, especially progressive myopia, usually transient and reversible after stopping HBO2 sessions, or pulmonary dyspnea, with cough and inspiratory pain. More serious O2-induced seizures happen rarely, at higher O2 pressures, and often during acute treatments in acidotic patients (carbon monoxide poisoning).

Seizure incidence by treatment pressure in patients undergoing hyperbaric oxygen therapy.

INTRODUCTION: Hyperbaric oxygen (HBO2) therapy uses different maximum treatment pressures. A side effect of HBO2 is oxygen toxicity seizure. The purpose of this study was to determine the overall incidence of oxygen toxicity seizure and assess risk at different treatment pressures. METHOD: A retrospective chart review was performed on patients who underwent HBO2 at a university hospital and at an outpatient center. Statistical analysis was performed to determine overall incidence of seizure and identify risk factors including maximum treatment pressure. RESULTS: A total of 931 patients were identified representing a total of 23,328 treatments. The overall incidence of seizure was one in 2,121 treatments (five per 10,000). There were zero per 10,000 at 2.0 atmospheres absolute/atm abs (0/16,430), 15 per 10,000 at 2.4/2.5 atm abs (1/669) and 51 per 10,000 at 2.8 atm abs (1/197). There was a statistically significant difference for seizure between the different pressures (χ2 (2, 23,540) = 31.38, p < .001). DISCUSSION: The overall incidence of oxygen toxicity seizure in this study is consistent with recent reports. This study demonstrated a statistically significant increased risk of seizure with increasing treatment pressure. Treatment at higher pressure should be chosen based on demonstrable benefit with a clear understanding of increased risk with higher pressure.

Incidence of DCS and oxygen toxicity in chamber attendants: a 28-year experience.

Decompression sickness (DCS) and central nervous system oxygen toxicity are inherent risks for "inside" attendants (IAs) of hyperbaric chambers. At the Hyperbaric Medicine Center at the University of California San Diego (UCSD), protocols have been developed for decompressing IAs. Protocol 1: For a total bottom time (TBT) of less than 80 minutes at 2.4 atmospheres absolute (atm abs) or shallower, the U.S. Navy (1955) no-decompression tables were utilized. Protocol 2: For a TBT between 80 and 119 minutes IAs breathed oxygen for 15 minutes prior to initiation of ascent. Protocol 3: For a TBT between 120-139 minutes IAs breathed oxygen for 30 minutes prior to ascent. These protocols have been utilized for approximately 28 years and have produced zero cases of DCS and central nervous system oxygen toxicity. These results, based upon more than 24,000 exposures, have an upper limit of risk of DCS and oxygen toxicity of 0.02806 (95% CI) using UCSD IA decompression Protocol 1, 0.00021 for Protocol 2, and 0.00549 for Protocol 3. We conclude that the utilization of this methodology may be useful at other sea-level multiplace chambers.

Oxygen: the poison is in the dose.

Cell-free hemoglobin (Hb) has been blamed for a spectrum of problems, including vasoconstriction pancreatitis, myocardial infarction, and pulmonary hypertension in hemolytic anemia, malaria, and sickle cell anemia, and from Hb-based oxygen carriers (HBOCs). Toxicities have been attributed to scavenging of nitric oxide (NO). However, while NO scavenging may explain many in vitro effects, and some effects in animal models and clinical trials with HBOCs, key inconsistencies in the theory require alternative explanations. This review considers the hypothesis that cell-free Hb oversupplies oxygen to tissues, leading to oxygen-related toxicity, possibly through formation of reactive oxygen species and local destruction of NO. Evidence for this hypothesis comes from various sources, establishing that tissue oxygen levels are maintained over very narrow (and low) levels, even at high oxygen consumption. Tissue is normally protected from excessive oxygen by its extremely low solubility in plasma, but introduction of cell-free Hb, even at low concentration, greatly augments oxygen supply, engaging protective mechanisms that include vasoconstriction and ischemia. The requirement to limit oxygen supply by cell-free Hb suggests novel ways to modify it to overcome vasoconstriction, independent of the intrinsic reaction of Hb with NO. This control is essential to the design of a safe and effective cell-free HBOC.

The use of medical orders in acute care oxygen therapy.

The life of every living organism is sustained by the presence of oxygen and the acute deprivation of oxygen will, therefore, result in hypoxia and ultimately death. Although oxygen is normally present in the air, higher concentrations are required to treat many disease processes. Oxygen is therefore considered to be a drug requiring a medical prescription and is subject to any law that covers its use and prescription. Administration is typically authorized by a physician following legal written instructions to a qualified nurse. This standard procedure helps prevent incidence of misuse or oxygen deprivation which could worsen the patients hypoxia and ultimate outcome. Delaying the administration of oxygen until a written medical prescription is obtained could also have the same effect. Clearly, defined protocols should exist to allow for the legal administration of oxygen by nurses without a physicians order because any delay in administering oxygen to patients can very well lead to their death.

Epilepsy and recreational scuba diving: an absolute contraindication or can there be exceptions? A call for discussion.

Recreational scuba diving is a popular sport, and people with epilepsy often ask physicians whether they may engage in diving. Scuba diving is not, however, without risk for anyone; apart from the risk of drowning, the main physiological problems, caused by exposure to gases at depth, are decompression illness, oxygen toxicity, and nitrogen narcosis. In the United Kingdom, the Sport Diving Medical Committee advises that, to dive, someone with epilepsy must be seizure free and off medication for at least 5 years. The reasons for this are largely theoretical. We review the available evidence in the medical literature and diving websites. The risk of seizures recurring decreases with increasing time in remission, but the risk is never completely abolished. We suggest that people with epilepsy who wish to engage in diving, and the physicians who certify fitness to dive, should be provided with all the available evidence. Those who have been entirely seizure-free on stable antiepileptic drug therapy for at least 4 years, who are not taking sedative antiepileptic drugs and who are able to understand the risks, should then be able to consider diving to shallow depths, provided both they and their diving buddy have fully understood the risks.