Review of world literature

Vladan Stanojković, otorinolaryngologists and the first expert in hyperbaric and diving medicine in Slovenia with the permission of ZZS and the Ministry of Health

OXYMED POLIKLINIKA d.o.o

Tomažičev trg 2

Koper, 6000

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INTRODUCTION:

The use of HBOT for the treatment of COVID-19 is supported by various international clinical trials and recognized by the World Health Organization as a non-drug treatment for COVID-19. For the purposes of a definitive validation at a national level, in accordance with specific legislation in each country of application, clinical trials are currently underway across Europe, Middle East and North America. Whilst a scientific discussion involves the presentation of thorough clinical documentation, that is not the purpose of this page.

Meanwhile, Dr. Serena is collecting data from doctors across the country and says he’s already seeing an even higher recovery rate for patients who receive HBOT. “It seems to work in 80%,” Dr. Serena said, pausing to add, “80 to 90% range.”

Yet, Dr. Harch says many doctors who are struggling with the decision of placing a patient on a ventilator aren’t even aware of the HBOT option. And while scientific studies are costly and slow, even the doctors committed to the skepticism of rigorous review remain optimistic.

PROVEN EFFECTIVENESS OF HBOT IN TREATING COVID-19

COMMENT:

Primarius dr med. Miodrag Zivkovic, specialist in maritime, hyperbaric and underwater medicine, physiologist says:

Let's start with the lungs:

1. A viral respiratory infection that primarily attacks pneumocyte 2 which has the role of producing a surfactant which plays a key role in the transport of oxygen across the alveolar-capillary membrane. The surfactant has a triple role: To maintain optimal surface tension in the alveoli and ensure that the alveoli are open thereby ensuring alveolar ventilation and oxygen supply to the alveolar-capillary membrane. That the phosphoglycerol compounds from the surfactant accept oxygen and deliver it to the erythrocytes in the blood capillaries of the lungs by facilitated diffusion. Recent research shows that pneumocyte 2 produces hemoglobin that probably binds oxygen during transport across the alveolocapillary membrane? To keep the influx of foreign particles and microorganisms that reach the lungs from the outside environment, prevent the penetration into the bloodstream or lung tissue and expel that content out of the lungs (cough). The consequences of pneumocyte 2 damage and impaired surfactant production are significantly reduced oxygen transport due to pulmonary atelectasis, thickening of the alveolar-capillary membrane and lack of surfactant as an oxygen carrier. This causes general hypoxia of lesser or greater intensity, which requires the fight against hypoxia. All the above pathological factors plus pulmonary hypoxia lead to interstitial, then aveolar edema and finally to ARDS. At the beginning of the pandemic, American doctors started using HBO on 40 patients with severe pneumonia at high pressure (2.0 bar, 60 min). We are waiting for the first reports. In Sweden, they started a multicenter study on 200 moderately severe patients at also high oxygen pressures of 2.4 bar (14 m depth, 100% oxygen) for 30 to 60 min. We are waiting for the first reports. Doctors in Russia routinely use HBO in the treatment of severe forms of pneumonia (viral, bacterial) at low partial pressures and short exposures (30 to 45 min). There are no reports yet.

Dr. Zivkovic says : my suggestion is as follows: Treatment of viral pneumonia is in the first place decisive reoxygenation with the use of hyperbaric oxygenation at medium and low partial pressures depending on the severity of the disease (1.2 to 1.5 bar), but long lasting up to 120 minutes and repeated treatment two to three times a day. Why is HBO the therapy of choice over a respirator? because the general pressure in the lungs is equal to the ambient pressure and there is no mechanical damage to the lungs as with a respirator. The use of surfactant (pig, beef) should also be considered here, as in the case of ARDS in preterm infants. 2. Another problem with SARS-COVID 2 virus infection is a component of the virus with gene particles that primarily attack pneumocyte 2, leading to the destruction of erythrocytes and the release of large amounts of iron into both plasma and tissues. The decrease in hemoglobin and the number of erythrocytes in the systemic circulation drastically deepens the already existing hypoxia, which endangers the function of organs particularly sensitive to hypoxia (brain, kidneys, heart, ...). The problem is complicated by patients who already have chronic hypoxia (cardiovascular diseases, diabetes and other metabolic diseases and hereditary diseases of respiratory enzyme dysfunction or mitochondria). The problem is complicated. Therapeutically speaking, reoxygenation is still crucial and again I prefer hyperbaric oxygenation, but here we must jump in with the use of erythropoietin alpha or beta (Recormon is available on our market). Erythropoietin is an erythrocytopoietic growth factor and acts on the bone marrow by increasing erythrocyte production. What is the advantage of giving erythropoietin: it increases the production of erythrocytes and the amount of hemoglobin and consumes the excess iron from the circulation caused by the breakdown of erythrocytes and thus reduces the toxic effect of iron.

3. Of course, continue with antibiotic therapy and correct symptomatic disorders with high doses of antioxidants. 4. I would like to clarify a bit the role of HBO in all this: Antihypoxic role. It is clear that HBO is the therapy of choice in all acute hypoxic diseases and in serious chronic hypoxic diseases. Anti-inflammatory effect because it stops the production of IL1b and TNF. Regenerative because it significantly stimulates the production of stem cells. Indirect antibacterial and antiviral action because it enables optimal activity of the cellular immune system. It changes the rheological characteristics of blood by reducing platelet aggregation and the interaction of platelets and leukocytes, which reduces the possibility of blood clots in blood vessels (coagulation). It increases the elasticity of erythrocytes and their easier passage through capillary blood vessels. Essential effect on the energy status of the cell and the organism as a whole.

My respect. Prim Dr. Miodrag Zivkovic

*Very impressive analysis of COVID-19 issue by prof. Sharif Sultan (President of the International Society of Vascular Surgery)* 16.04.2020:

Based on observations in USA, Spain, Italy, France and UK, and from postmortem of lungs involvement in COVID 19, all revealed pulmonary thrombosis which is not typical ARDS , but more alarming that it is patient hypoxemia that is not responding to PEEP but high oxygen flow.

Like methemoglobin, the COVID 19 virus structural protein, sticks to heme – displaces oxygen – which release iron-free ion , that leads to toxicity and causes inflammation of alveolar macrophages- that results in bilateral CT scan changes as it is a systemic response.

There is no benefit of invasive ventilation, but patients may require frequent blood transfusions or plasmapheresis.

The COVID 19 virus attacks beta chain, dissociates heme, removing iron and converting it to porphyrin. The virus can dissociate oxy-Hb, carboxy-Hb and glycosylated Hb.

Lung inflammation results from the inability of both oxygen and CO2 exchange, leading to the ground glass on x rays, it mimics CO2 poisoning as an invisible enemy.

Chloroquine competes for the binding to porphyrin.

Favipiravir binds to the virus envelope protein with very high affinity, prevents entry into the cells as well as binding of the structural protein to porphyrin.

If free radicals scavengers and iron chelating agents are added to the protocol of management, it may lessen the inflammation process.

COVID 19, SARS2 is not ‘pneumonia’ nor ARDS. Invasive ventilation is not only the wrong solution, but emergency intubation can harm and result in more damage, not to mention complications from tracheal scarring and stiff lung during the duration of intubation.

Furthermore, a new treatment protocol needs to be established, so we stop treating patients for the wrong disease.

COVID-19 causes prolonged and progressive hypoxia by binding to the heme groups in the red blood cells.

People are desaturating due to failure of the blood to carry oxygen.

This will lead to multi-organ failure and high mortality.The lung damage seen on CT scans is due to the oxidative iron released from the haemolysed red blood cells which in turn overwhelm the natural defences against pulmonary oxidative stress and causes what is known as Cytokine storm.

There is always-bilateral ground-glass opacity in the lungs. Recurrent admission for post-hypoxic leukoencephalopathy fortifies our findings that COVID-19 patients are suffering from metabolic hypoxia due to blood capacity failure.

COVID-19 glycoproteins bond to the heme in RBC, and in doing so, the toxic oxidative iron ion is disassociated and released. The freely roaming iron in the blood without any physiological function will culminate into the following;

1) Without the iron ion, haemoglobin can no longer bind to oxygen. Once the haemoglobin is impaired, the red blood cell is essentially none functioning in carrying and delivering oxygen to any tissues.

RBC’s Become useless and a burden on the patients as they circulate around with COVID-19 virus attached to its porphyrin. This lead to the destruction of the red blood cells and the patient’s oxygen saturation levels drop significantly.

What is happening equates to carbon monoxide poisoning, in which carbon monoxide is bound to the haemoglobin with the failure of gas exchange.

Ventilations will not manage the root cause, which is blood organ failure.

COVID 19 patients, unlike CO poisoning in which eventually the CO can break off, the affected haemoglobin is permanently stripped of its ability to carry oxygen where the body compensates by secreting excess erythropoietin to stimulate the bone marrow to secrete new red blood cells. This is the reason we will find thrombocytosis and decreased blood oxygen saturation as one of the three primary indicators of COVID 19 severity score.

2) The freely floating iron ion are highly reactive and causes oxidative damage. This always happens physiologically and naturally to a limited extent in our bodies and such cleanup is a defence mechanism to keep the balance.

The three primary Lung defences to maintain “iron homeostasis”, 2 of them are in the alveoli.

The first of the two are macrophages that roam around and scavenge up the free radicals of the oxidative iron. The second is a lining on the epithelial surface which has a thin layer of fluid packed with high levels of antioxidant molecules such as ascorbic acid (Vitamin C) among others.

When too much iron is in circulation, it begins to overwhelm the lungs’ counter measures begins, the process of pulmonary oxidative stress. This leads to damage and inflammation, which leads to the so-called Cytokine storm; this can be documented on high-resolution CT scans of

In COVID-19 patient lungs, It is a fact that it affects both lungs at the same time and Pneumonia rarely ever does that, but COVID-19 does every single time.

The liver is attempting to do its best to remove the iron and store it in its ‘iron vault’. Only its getting overwhelmed too. It is starved for oxygen and fighting a losing battle from all the haemolysis haemoglobin and the freed iron ion. The liver will start releasing alanine aminotransferase (ALT) which is the second of 3 primary COVID 19 severity score indicators.

A patient must be managed on maximum oxygen flow through a hyperbaric chamber on 100% oxygen at 1, 2 to 1.5 ATA pressure, for 90-120 minutes twice or three times per day for minimum five days.

This is in order to give what has left of their functioning haemoglobin a chance to carry enough oxygen to the organs and keep them alive.

We do not have nearly enough of those hyperbaric chambers.

Blood transfusion with packed fresh red blood cells to patients after plasmapheresis may ameliorate the cytokine storm.

The main point that patients will require ventilators if they present late with multi-organ system failure to tie them over this life or death scenario. However, intubation is futile unless the patient’s immune system modulates the situation. We must address the root of the illness and avoid using traditional teachings to manage a failing system.

If we reach the inevitably to ventilate, it must be done at low pressure but with maximum oxygen flow. We must avoid tearing up the lungs with maximum PEEP as we are doing more harm to the patient because we are managing the wrong organ.

There is a small village in northern Italy where the majority of its population suffers from thalassemia. They had no deaths and no cross-community spread. Moreover, parts of Nepal which are 1km above sea level are COVID-19 free. All points that we are chasing the wrong organ; it is not the lungs; it is a blood problem.

In healthy people, the virus is normally eliminated by nitrogen monoxide and oxygen free radicals.

Over 50% of mortality in (non-HBOT treated) COVID-19 patients has occurred in those with pre-existing dysmetabolic hypercholesterolaemia, diabetes, obesity and/or cardiovascular diseases related to impaired normal endothelial function and reduced production of nitrogen monoxide.

In patients with comorbidities, hyperbaric oxygen therapy restores the normal synthesis of nitrogen monoxide (through the genetic expression of Nitric Oxide Synthase) allowing the body to eliminate the virus as it does in a healthy person. This genetic activation (up-regulation) is reinforced by the implementation of a cycle of HBOT sessions. All patients with high-risk comorbidities who began HBOT prior to, or in the initial stages of, hospitalization have made a full recovery. In clinical trials to date, every critically ill COVID-19 patient in intensive care that was treated with hyperbaric oxygen therapy has made a full recovery. Nevertheless, early treatment is always advisable for an effective recovery that prevents viral progression necessitating intensive care.

Outcomes, of course, are largely dependent on the severity of any pre-existing conditions (comorbidities) known to be high-risk factors in connection with COVID-19. Having said that, of the dozens of critically ill patients who have accessed a cycle of HBOT, most also had multiple pre-existing high-risk factors (for COVID complications) such as diabetes, heart disease and obesity – and, even so, all recovered.

HBOT means that the patient is under high pressure. The common metaphor of the difference between breathing mode and atmospheric pressure is that breathing on the plateau is the same as breathing on the plain, which is natural breathing. Different from mechanical ventilation, it has a great effect on respiratory tract, need to be paid attention to and dealt with by doctors and nurses at all times. Otherwise, it is easy to have various complications such as an-way Injury.

Fifthly, there is no conflict with the current means of critical treatment, and the +HBOT mode has a clear role in improving the treatment effect.

COVID-19, in addition to antibodies and vaccines, there is no specific drug. All clinical treatment is basically symptomatic treatment and supportive treatment. HBOT is not the etiological treatment of COVID-19, it is the symptomatic treatment of hypoxia in patients with COVID-19, and it is a supplement to the existing oxygen treatment technology. In addition to HBOT once a day for 95-120 minutes, the patients also received the existing comprehensive treatment in ICU, including mechanical ventilation. In addition to HBOT, ICU clinicians are still responsible for the daily comprehensive treatment of the above-mentioned severe patients. There is no conflict in treatment technology. On the contrary, it can provide better support for other supportive treatments.

CONCLUSION: We recommend the following :

1. Inhibit viral growth and replication by the adjuvant use of CHQ+ZPAK+ZINC or other retroviral therapies being studies. The less virus load we have, the less haemoglobin is losing its iron, the less severity and damage with the prevention of cytokine storm.

2.Hyperbaric medicine utilization in any shape or form for anyone with thrombocytosis and elevated ALT can prevent the rapid ascent to the abyss.

3. Plasmapheresis and Blood transfusions will give supportive symptomatic relief.

4. No international travel until an effective vaccine is available.

5. Cessation of tobacco, vaping and alcohol products.

Stay safe and self isolate