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Medical Specialties

Hyperbaric medicine

Definition

Hyperbaric oxygen therapy is a treatment by which a patient breathes 100% O2 while inside a hyperbaric chamber, at a pressure higher than the atmospheric pressure (> 1 atm). In certain circumstances, it represents the first therapeutic indication, and in others, it serves as an adjuvant to surgical or pharmacological interventions.
Oxygen is a colorless, odorless gas that constitutes approx. 21% of the Earth's atmosphere. It is essential to life for two reasons:
Oxygen is one of the basic structural elements of the body. All the main components - water, proteins, fats, carbohydrates - contain oxygen. Oxygen is necessary for the chemical reactions in the body that produce energy.

How does it work

Hyperbaric medicine is effective for a multitude of disorders, as it determines the following basic actions:
• additional oxygenation of the body through the diffusion of oxygen into the blood plasma and subsequently into all the fluids of the body, increasing up to 6 times the availability of O2 for tissues (table 1)
• increases the antimicrobial capacity of the body to fight infections
• stimulates the creation of new capillaries
• increases anti-inflammatory tissue perfusion
• improves the overall metabolic level
• stimulates the production of red blood cells
• stimulates the production of stem cells (up to 400% after 40 sessions)
• reduces edema
• increases the rate of healing in chronic lesions (e.g. skin ulcers)
A person exposed to hyperbaric oxygen therapy has up to 20 times oxygen dissolved in arterial blood, and other biological fluids, such as the cerebrospinal fluid, are also perfused with additional oxygen. Hemoglobin is not additionally loaded, as it already is at maximum capacity (arterial blood, 9599% Hb saturation). Oxygen diffuses from the capillaries into the tissues and reaches the weakly perfused or non-perfused areas. According to the Kogh diffusion coefficient, more oxygen is supplied to the tissues through diffusion than through the bloodstream.
The overall effect is that of hyperoxygenation of the body, therefore the process is called hyperbaric oxygen therapy.
The hyperbaric chambers that are used are accredited at European level (EN 14931 MedCert).

Medical Procedure

The treatment may be carried out in an enclosure for one or more patients. Our clinic uses a single-place hyperbaric chamber, as well as a multi-place one for 4 people. Pressurization is achieved by atmospheric air, and the patient breathes O2, administered through a comfortable mask and a breathing system with adequate flow to the current respiratory volume (BIBS-build in breathing system) which will ensure a relaxed posture during therapy. At the beginning of the therapy, there is a pressurizing noise of the air entering the chamber. During the treatment and particularly in the first minutes, the ears may be clogged, similar to the sensation when the plane takes off, and gentle maneuvers are required, to balance the pressure between the middle and outer ear, through rotational mandibular movements, by yawning, swallowing, by applying the Valsalva maneuver. The doctor will assist the patient throughout the treatment. Towards the end of the treatment, the pressure in the hyperbaric chamber starts decreasing, slightly returning to the normal one.
An example of therapy is shown in Fig. 1. Table 9 is used by the U.S. Navy, as it is one of the most used therapies alongside other specific decompression maneuvers. During this treatment, the patient initially breathes atmospheric air as the pressure in the room increases accordingly at a rate of about 2 meters of sea water (msw) per minute. The therapeutic range of 13.5 -20 msw is reached, after which the patient breathes 100% oxygen in the first 30-minute step. There is an air break of 5 minutes, followed by treatment with the second stage of 30 minutes of oxygen. Finally, the "surface lift" - decompression, is performed, also at a rate of 2 msw/min. This treatment may be adjusted as duration and as maximum pressure level depending on the clinical condition and on the prevailing condition.
 
Therapy has 3 stages: a) compression, which lasts for approximately 15 minutes, b) the actual treatment session, with the duration calculated according to the treatment, c) decompression, with the same duration as the compression.
Depending on the diagnosis, a type of treatment will be chosen with a pressurization level (depth of immersion) between 2 and 3 ATA (absolute atmosphere - atm + ordinary atmosphere) and rigorously calculated exposure times maintained during therapy (1, 2, 3 hours).
During the session with hyperbaric oxygen, the air pressure in the room reaches a value of two, up to three times, higher than normal. This increase in pressure will cause a temporary sensation of ear clogging, similar to that felt during a plane take-off or when reaching high altitudes. This sensation may be reduced by yawning or swallowing. In order for the effects of oxygen therapy to settle, the patient will most likely undergo several treatment sessions. The number of sessions depends on the patient's medical condition. For certain conditions, such as carbon monoxide poisoning, three treatment sessions are required. Other conditions, such as wounds that are difficult to heal, require 10 to 20 treatment sessions. As regards neurological disorders, for a partial/total recovery, between 20 and 40 consecutive sessions are required, 1-2 per day, 5-6 days per week, depending on the condition of each patient.
Hyperbaric oxygen therapy is extremely effective and therefore recommended as a unique treatment for decompression disease, arterial embolism and severe carbon monoxide poisoning.
To enhance the efficiency of treating other conditions, hyperbaric oxygen therapy can be part of a comprehensive treatment plan and may therefore be administered jointly with other therapies and medicines.

Short history

Hyperbaric medicine refers to the medical treatment during which an atmospheric pressure with a value greater than that of sea level is used (about 760 mmHg). The treatment describes hyperbaric oxygen therapy (HBOT), namely the medical use of oxygen at an atmospheric pressure which is higher than the normal atmospheric pressure, and therapeutic reprocessing, aimed at reducing the harmful effects of gas bubbles, by physically reducing their size, and ensuring optimal conditions. eliminating them and the excess gas dissolved in the blood.
The first hyperbaric chamber was built in 1662 by Nathaniel Henshaw, a British physician and clergyman - a sealed chamber, called domicilium, inside which the intended pressure was reached by means of bellows and valves. He believed that using pressure could help treat certain respiratory diseases.

In the 18th and 19th centuries, more and more doctors began to introduce compressed air in their medical practice in order to increase oxygenation in patients, to such an extent that, in 1877, documents showed that hyperbaric chambers were used to treat a wide range of health issues.

In 1861, the American neurologist James Leonard Corning built the first hyperbaric chamber ever used in the United States. He used the device to treat workers who were working on the building of the Hudson tunnel in New York and who had suffered from severe decompression following the excavations executed under the sea level.

And in 1917, German inventors Heinrich and Bernhard Dräger treated, for the first time, by using under pressure oxygen, the divers suffering from decompression. Beginning with the 1940s, hyperbaric oxygen treatment has become a standard treatment for US military divers. Scuba divers who come to the surface too quickly are exposed to the risk of decompression sickness (DCS), sometimes called "the bends" or arterial gas embolism. These phenomena are known as decompression sickness and both refer to issues that occur with the air in the body. The consequences can be severe, and HBOT is the primary treatment for both conditions.

In the same first half of the 20th century, Dr. Orville Cunningham, from Kansas, USA, used HBOT to treat patients with severe forms of influenza who were not responding to any treatment. However, it was only in the 1950s that hyperbaric oxygen therapy started being used on a broader scale.

Today, US metropolitan hospitals and treatment clinics are using hyperbaric oxygen therapy in the treatment of degenerative disorders and of those that lower the oxygen concentration of the blood. Currently, the FDA has approved the use of HBOT for 14 conditions. And, while some researchers continue to challenge its effectiveness, for decades, doctors in Europe, Russia, Mexico, China and the US have used HBOT to successfully treat a variety of serious health conditions.

How does it work in the body

Hyperbaric oxygen therapy implies the inhaling of pure oxygen in a pressurized chamber or cabin. In addition to the applications in the decompression sickness of divers, hyperbaric oxygen therapy is also a treatment for other conditions such as serious infections, wounds that are difficult to heal, complications of diabetes or radiotherapy.

In a hyperbaric oxygen therapy chamber, the air pressure is increased until it reaches values that are three times higher than those of normal air pressure. In these conditions, more pure oxygen is concentrated in the lungs, compared to the oxygen level at normal air pressure values.

This increased amount of oxygen is carried through the blood vessels in the entire body. The increased concentration of systemic oxygen helps the body fight bacteria and at the same time stimulates the synthesis and release of growth factors and stem cells, which promotes tissue regeneration and healing.

Recommendations

US Hyperbaric Medical Society  
•    Arterial gas embolism
•    CO poisoning (carbon monoxide)
•    Gaseous gangrene (myositis with Clostridium pertfringens type A, myonecrosis)
•    Compartment syndrome, acute trauma by crushing
•    Decompression sickness
•    Arterial or venous insufficiency
•    Central retinal artery occlusion
•    Acute hearing loss, Meniere's disease, complicated chronic external otitis
•    Severe anemia
•    Intracranial abscess
•    Necrotizing soft tissue infections
•    Skin ulcers
•    Osteomyelitis
•    Post-radiotherapy lesions (bone, soft tissue necrosis)
•    Compromised skin grafts

Summary of international indications for HBOT:
•    Recovery in spastic hemiplegia after stroke, paraplegia,  
•    Myocardial insufficiency, peripheral vascular disease
•    Embolism
•    Asphyxiation: drowning, smoke inhalation, etc.
•    Cardiovascular diseases and post cardiac surgery
•    Decompression sickness
•    Dentistry: refractory periodontitis, adjuvant implant therapy
•    Endocrine: diabetes, diabetic foot
•    Radiotherapy
•    Gastrointestinal: gastric ulcer, necrotizing enterocolitis, paralytic ileus, hepatitis
•    Head and neck surgery: osteoradionecrosis and osteomyelitis of the jaws
•    Hematology: severe anemia
•    Pulmonary diseases: pulmonary abscess, pulmonary embolism (adjuvant to surgery)
•    Neurological: stroke, multiple sclerosis, migraine, cerebral edema, multi-infarct dementia, spinal-cord injury and vascular diseases of the spinal cord, brain abscess, peripheral neuropathy, radiation myelitis, vegetative coma
•    Obstetrics: complicated pregnancy - diabetes, eclampsia, heart diseases, placental hypoxia, fetal hypoxia, congenital heart disease of the newborn
•    Ophthalmology: central retinal artery occlusion
•    Orthopedics: non-unification of fractures, bone grafts, osteoradionecrosis
•    Otolaryngology: sudden deafness, acute acoustic trauma, labyrinthitis, Meniere's disease, malignant otitis externa (chronic infection)
•    Peripheral vascular disease: ischemic gangrene, critical limb ischemia
•    Plastic and reconstructive surgery: for the healing of wounds that do not heal
•    survival of cutaneous flows with marginal circulation, as an aid in reimplantation surgery and as an aid in the treatment of burns
•    Poisoning: carbon monoxide, cyanide, etc.
•    Traumatology: crushing injuries, compartment syndrome, etc.
•    Treatment of certain infections: gangrene, acute necrotizing fasciitis, refractory mycosis, osteomyelitis

Benefits


The effects of hyperbaric oxygen therapy are based on gas laws and on the physiological and biochemical effects of hyperoxia.

Boyle's law states that, at a constant temperature, the pressure and volume of a gas are inversely proportional. This is the basis of many effects of hyperbaric therapy, including a slight increase of the room temperature during treatment, but also the phenomenon known as "squeezing" – it occurs when blockages in the Eustachian tube prevent gas pressure equalization, causing the painful gas compression in the middle ear.

Dalton's law states that, in a mixture of gases, each element exerts a pressure proportional to the fraction of the total volume (partial pressure).

Henry's law states that, at constant temperature, the amount of gas dissolved in a fluid or tissue, at saturation, varies directly proportionally to the partial pressure of the gas in contact with the fluid or tissue. This law is the basis of the increased oxygen saturation in tissues in HBOT treatments. Nevertheless, it has implications (and risks) on the need for decompression of the other patients located in multi-place chambers, as their inert gas concentrations (especially nitrogen) will also be increased. The risk consists in the nitrogen that dissolves in the blood and that may form arterial gas bubbles during depressurization.

Most of the oxygen carried in the blood is bound to hemoglobin, which, at normal atmospheric pressure, is 97% saturated. However, some of the oxygen is also carried freely (in solution), and during treatment, as a result of Henry's law, this volume is increased, maximizing tissue oxygenation. When we breathe air at normal values of atmospheric pressure (1 ATA), the blood pressure is of approximately 100 mmHg and the oxygen tension in the tissues is of approximately 55 mmHg. However, a 100% oxygen saturation at 3 ATA can increase blood pressure to 2000 mmHg and tissue oxygen tension to approximately 500 mmHg, allowing 60 ml of oxygen per liter of blood to be released (compared to 3 ml/l at a normal atmospheric pressure), which is enough to support the function of poorly oxygenated tissues without a contribution of oxygen from hemoglobin. Because the solution contains oxygen, it can also reach the physically obstructed areas, where red blood cells cannot reach, and it can also allow tissue oxygenation even in cases of severe anemia or carbon monoxide poisoning.

Hyperbaric oxygen therapy stimulates the synthesis of oxygen-free radicals, which oxidize membrane proteins and lipids, affect DNA integrity and inhibit bacterial metabolic functions. HBOT is particularly effective against anaerobic organisms (which do not need oxygen to survive) and stimulates the function of oxygen-dependent peroxidases by which leukocytes destroy bacteria in the body. Hyperbaric oxygen therapy also improves the oxygen-dependent transport of certain antibiotics through the walls of bacterial cells.

HBOT optimizes wound healing processes by amplifying oxygen gradients along ischemic wounds and by promoting matrix-dependent, oxygen-dependent collagen formation, necessary for angiogenesis.

During reperfusion (restoring blood flow through an artery that was previously occluded through a pathological process), leukocytes adhere to ischemic tissues, releasing proteases and free radicals, leading to pathological vasoconstriction and tissue destruction. This exacerbates wounds and compartmental syndromes, increasing the risk of rejection of grafts and reconstruction procedures. It has been found that this injury caused by free radicals is also involved in neuronal injury caused by ischemic accidents, exposure to toxic substances and certain drugs. Specifically, reduced leukocyte adhesion and post-ischemic vasoconstriction has been proven (both are tissue repair processes), in the case of HBOT treatment in ischemic rat tissue, as well as a decrease in lipid peroxidation, in cases of carbon monoxide poisoning.

Hyperoxia of healthy tissues, determined by the hyperbaric treatment, causes quick vasoconstriction, but it is compensated by increased plasma oxygen transport and thus microvascular blood flow to ischemic tissue is actually enhanced by HBOT. Moreover, this vasoconstriction reduces post-traumatic edema, contributing to increased healing processes of crush injuries, compartment syndromes and burns.

Finally, we note that hyperbaric oxygen therapy prevents the decrease of post-ischemic ATP production and decreases the accumulation of lactate in the ischemic tissue, both situations stimulating the processes of recovery and healing.

Therefore, HBOT has complex effects on the immune function, on oxygen transport and on hemodynamics. The positive therapeutic effects result from the reduction of hypoxia and edema, which allows a better response of the body in case of infections and ischemic accidents.

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Anti-tumoral effect

It is a well known fact that hypoxia is a common feature of different solid tumors. Local impairment of the circulatory system entails the generation of a heterogeneous population of tumor cells that are not normally supplied with oxygen and nutrients in most regions of the tumor, except those that are in close proximity to the blood vessels. The reduced cell division seen in areas with low oxygenation in tumors results in resistance to both radiotherapy and chemotherapy.

Furthermore, poorly vascularized areas of the tumor may be perfused, through sub-lethal levels, by cytotoxic agents, thus generating an acquired resistance to chemotherapy. A study published in Nature magazine has also shown that hypoxia may be responsible for a variety of growth modulation effects that could generate an advantage of cancer cell growth.

Yang and his research team found that the hypoxia-induced expression of factor-1 (HIF-1), suggested to be an endogenous marker of tumor hypoxia, significantly affected the overall survival and the disease-free survival of osteosarcoma patients.

HBOT dramatically increases the amount of oxygen dissolved in the plasma, oxygenates the hypoxic tissues and promotes neovascularization, eventually leading to increased blood flow. These features of hyperbaric oxygen therapy increase the partial pressure of oxygen inside the tumor and make it more susceptible to radiotherapy.

HBOT has been extensively and successfully used in radiotherapy to increase radiation sensitivity and tumor oxygenation. In the same way, hyperbaric oxygen therapy enhances the perfusion of chemotherapeutic agents into hypoxic tumors and the susceptibility of tumor cells to such drugs.
 
Several studies have suggested that hyperbaric oxygen therapy can promote the growth or recurrence of malignancy by promoting angiogenesis, while other studies have shown inhibitory effects on tumor growth. However, two independent research groups have recently reviewed experimental and clinical data from the literature of the past 50 years and concluded that intermittent exposure to HBOT had no stimulatory effects on primary or metastatic cancer growth.

Currently, HBOT is used clinically in combination with radiotherapy and chemotherapy as a treatment approach of malignant tumors.

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Bibliography



  • Textbook of Hyperbaric Medicine, Kewal K. Jain, Springer International Publishing AG 2017, 6th Edition, ISBN 978-3-319-47138-9 ISBN 978-3-319-47140-2 (eBook), DOI 10.1007/978-3-319-47140-2
  • Hyperbaric Oxygen Therapy Indications, 13th edition, Lindell K. Weaver, Best Publishing Company, FL, ISBN 978-1930536-73-9, 2014
  • Physiology and Medicine Of Hyperbaric Oxygen Therapy, Tom S. Neuman, ISBN 978-1-4160-3406-3, 2008
  • Handbook on Hyperbaric Medicine, Daniel Mathieu, Springer, ISBN-13 978-1-4020-4376-5, 2006
  • Mader JT, Adams KR, Couch LA, et al. Potentiation of tobramycin by hyperbaric oxygen in experimental Pseudomonas aeruginosa osteomyelitis (Abstract 1331). Abstracts of the 27th Interscience Conference on Antimicrobial Agents and Chemotherapy. Washington, DC, American Society for Microbiology 1987.
  • Hunt TK. The physiology of wound healing. Ann Emerg Med 1988; 17:1265–73.
  • Knighton DR, Silver IA, Hunt TK. Regulation of wound-healing angiogenesis—effect of oxygen gradients and inspired oxygen concentration. Surgery 1981; 90:262–70.
  • Weiss SJ. Tissue destruction by neutrophils. N Engl J Med 1989; 320:365–76.
  • Myers RAM. Hyperbaric oxygen therapy for trauma: crush injury, compartment syndrome, and other acute traumatic peripheral ischaemias. Int Anesthesiol Clin 2000; 38:139–51.
  • Zamboni WA, Roth AC, Russell RC, Graham B, Suchy H, Kucan JO. Morphological analysis of the microcirculation during reperfusion of ischaemic skeletal muscle and the effect of hyperbaric oxygen. Plastic Reconstr Surg 1993; 91:1110–23.
  • Thom SR. Antagonism of carbon monoxide-mediated brain lipid peroxidation by hyperbaric oxygen. Toxicol Appl Pharmacol 1990; 105:340–4.
  • Villanucci S, Di Marzio GE, Scholl M, et al. Cardiovascular changes induced by hyperbaric oxygen therapy. Undersea Biomed Res 1990; 17 (Suppl. 1):117.
  • Wattel F, Mathieu D, Neviere R, Bocquillon N. Hyperbaric therapy: acute peripheral ischaemia and compartment syndrome: a role for hyperbaric oxygenation. Anaesthesia 1998;53(Suppl. 2):63–5.