**4. Treating diseases with HBO**

*Respiratory Physiology*

a gas—and recommended staged decompression, especially at shallower depths. He prepared detailed practical dive tables for the Royal Navy to prevent acute decompression sickness. These guidelines remained the foundation of all diving operations until 1956 [10]. Heinrich Drager was the first to explore the use of pressurized oxygen in decompression sickness (**Figure 10**). His protocols were put into practice by Behnke and Shaw, who used HBOT for treating decompression sickness in the late 1930s. They replaced oxygen in place of compressed air, and their work resulted in the use of the first nitrogen-oxygen mixtures and hyperbaric treatment being tailored to the severity of the injury [11]. In 1939, the US Navy began treating divers suffering decompression sickness with hyperbaric oxygen therapy. After World War II, the US military conducted extensive research in HBOT, and this expanded the existing knowledge about survivable pressures and popularized HBOT in the late 1950s and early 1960s. In the 1980s, Paul Harch began an in-depth study of brain decompression illness (DCI) and evaluated divers with this disorder. He concluded that it was not residual gas that was being treated but ischemic brain injury. He went on to develop individualized treatment protocols for over 50 different chronic neurological disorders. Harch is considered to be the foremost authority in the use of HBOT and SPECT brain blood flow imaging in neurology [12–14]. In 1990, former microbiology professor Igor Gamow invented and patented the Gamow Bag that provided mountaineers with a mobile and effective method to treat high-altitude sickness. This bag is a single-place portable hyperbaric chamber, pressurized with a

**72**

**Figure 11.** *The Gamow Bag.*

**Figure 10.**

*Drager and his recompression chamber.*

In 1937, Brazilians Ozorio de Almeida and Costa pioneered the use of HBOT in treating leprosy [16]. In the 1950s, Ite Boerema, a cardiac surgeon from the Netherlands, conceived the idea of "flooding" the body's tissues with extra oxygen. Working with the help of the Royal Dutch Navy, Boerema conducted a series of animal experiments and operations within a hyperbaric oxygen chamber (**Figure 12**). These went off without a hitch and led to the installation of a large operating hyperbaric chamber at the University of Amsterdam. Many children with congenital heart diseases like tetralogy of Fallot, transposition of great vessels, and pulmonic stenosis were operated in this facility with great success. Boerema mooted the concept of "Life without blood" using HBO, when dissolved oxygen sufficed to meet the entire body's oxygen needs without the need for red cells or hemoglobin. Boerema is credited with being the father of modern-day hyperbaric medicine [17].

In 1955–1956, I Churchill-Davidson evaluated clinical trials on HBOT as a potentiator for radiation therapy in cancer patients at St. Thomas Hospital in London [18]. Public interest in hyperbaric oxygen therapy started to grow in the 1960s after publicity about its use in treating President John F Kennedy's sick infant. In 1961, a colleague of Boerema, W. H. Brummelkamp, published a paper on inhibition of anaerobic infections by HBOT [19]. In 1962, Smith and Sharp reported the enormous benefits of HBO in carbon monoxide poisoning. They recommended that all those having a verified carboxyhemoglobin level above 25% needed immediate HBOT at 3 ATA for 90 minutes, followed by two or three more sessions for full recovery, making HBO very cost-effective [20]. Global interest in HBOT was rekindled by this finding, resulting in hyperbaric units being installed at many centers like Duke University, New York Mount Sinai Hospital, Presbyterian Hospital and Edgeworth Hospital in Chicago, Good Samaritan in Los Angeles, St. Barnabas Hospital in New Jersey, Harvard Children's Hospital, and St. Luke's Hospital in Milwaukee. In 1965, Perrins from the UK demonstrated the effectiveness of HBOT

**Figure 12.** *Dr. Boerema with children operated by him.*

in osteomyelitis [21]. In 1966, Saltzman and coworkers from the USA proved the effectiveness of HBOT in stroke patients [22].

In 1970, Boschetty and Cernoch of Czechoslovakia conducted a trial of HBOT for multiple sclerosis. In their series 15 out of 26 patients with multiple sclerosis showed improvement after HBOT at 2 atmospheres [23]. In 1971, Lamm of West Germany used HBOT for treatment of sudden deafness. It was shown that HBOT shortens the course of healing in high-pitch perception dysacusis by upregulating constitutive nitric oxide synthase in the substructure of the cochlea [24]. In 1973, Thurston pioneered studies that showed lower mortality figures in patients with myocardial infarction treated with HBO. HBOT was shown to improve oxygen supply to the threatened heart and reduce the volume of infarct size and other major adverse outcomes [25]. In 1972, Richard A Neubauer set up the Ocean Hyperbaric Neurologic Center in Lauderdale-by-the-Sea exclusively for HBOT in the management of various central nervous system disorders. He mooted the concept of "idling" neurons capable of surviving for years or even decades after the original injury. He claimed that these injured neurons could be re-activated with HBOT and that the greater the number of idling neurons, the better would be the patient's response to HBOT [26]. Neubauer was also the co-founder and executive director of the American College of Hyperbaric Medicine. After his death in 2007 at the age of 83, his clinical research center in Florida was renamed the Neubauer Hyperbaric Neurologic Center. In 1976, Hollbach and Wasserman determined that 1.5 ATA (atmospheres absolute) maximizes oxygen content and glucose metabolism in the brain [27].

In 1985, RE Marx and his colleagues observed that the rate of osteoradionecrosis was 30%/patient in patients treated with penicillin alone while rates in those treated with HBO was only 5% [28]. In 1987, Jain successfully treated patients with paralytic stroke using HBOT [29, 30]. In 2002, a US Army study confirmed that HBOT repairs white matter damage in children with cerebral palsy. In 2005, Stoller of the USA treated the first case of a child with fetal alcohol syndrome using HBOT and with good outcome [31]. In 2006, Thom of the USA discovered that HBO causes stem cell mobilization [32]. In 2010, Godman discovered that HBOT activated 8101 genes, resulting in reduction of inflammation and increase in growth in body tissues [33, 34]. In 2011, Stoller treated the first retired National Football League (NFL) player for chronic traumatic encephalopathy [35]. In 2012, Harch and his colleagues demonstrated that blast-induced postconcussion syndrome and post-traumatic stress disorders responded to HBOT [15].


**75**

*Historical Aspects of Hyperbaric Physiology and Medicine*

The UHMS and FDA approved HBOT for treatment of conditions like autism, stroke, air embolism, ischemic limbs, split-thickness skin graft acceptance, failed grafts, flap survival and salvage, wound reepithelialization, acute thermal burns,

Many patients do not respond to aggressive acid-suppressing medications. HBOT has a beneficial effect in patients with blunt duodenal trauma, duodenal ulcers, and indomethacin-/radiation-induced gastritis. This salubrious effect is mediated by decreased production of oxidative stress markers like tumor necrosis factor-alpha, interleukin-1beta, neopterin, myeloperoxidase, and malondialdehyde. HBOT is seen to improve the acid-neutralizing function of the stomach, normalize gastric motility, reduce the duodenum acidification, decrease edema, and improve the blood flow both in human and equine studies [38, 39]. These effects were also

In September 1961, the First International Congress on the clinical applications of hyperbaric oxygen was held in Amsterdam. The Second International Conference on HBO was held in Glasgow in September 1964, with detailed deliberations on various aspects of HBOT. In November 1965, the Third International Congress on HBOT was organized at the Duke University at Durham, North Carolina. The Fourth and Fifth International Congresses were held in Sapporo,

Aberdeen, Scotland, hosted the sixth conference in August 1977. The subsequent International Congress was held in Moscow in 1981 and is an annual event thereafter. The deliberations during these academic forums threw fresh light on the basic physiology, oxygen toxicity, and therapeutic applications of HBO in

The Undersea Medical Society (it added hyperbaric to its name in 1986), an organization made up largely of naval and ex-navy physicians, was founded in 1967 in the USA. It reviewed the indiscriminate and inappropriate use of the HBO chamber for a variety of medical conditions by practitioners searching for a "cure-all" therapy, tarnishing the credibility of hyperbaric medicine. This nonprofit organization, now known as the Undersea and Hyperbaric Medical Society (UHMS), set up a Committee on Hyperbaric Oxygen Therapy in the 1970s to systematically review all the available scientific evidence for HBOT and formulate absolute indications for HBOT. This was accepted by insurance providers, including Medicare. The UHMS is committed to providing, promoting, developing, and raising the quality of care across the spectrum in scientific communication, life sciences, and clinical practices of hyperbaric medicine by promoting high standards of patient care and operational safety. It offers accreditation and certificate of competency and credibility and has over 2500 members in 50 countries. UHMS also awards board certification in Undersea and Hyperbaric Medicine through the American Board of Emergency Medicine (ABEM), the American Board of Preventive Medicine (ABPM), and fellowship training in Undersea and

In 1980, Dr. Richard A. Neubauer and Dr. William S. Maxfield formed the American College of Hyperbaric Medicine (ACHM) to foster the ethical advancement and expansion of hyperbaric medicine. The International Society of

Hyperbaric medicine was approved by the American Board of Medical Specialties as a sub-specialty of emergency and preventative medicine in 2000.

Japan, and Vancouver, respectively, in 1969 and 1973. The University of

seen in cases of inflammatory bowel diseases like Crohn's [40].

**5. Landmark academic events in HBOT**

*DOI: http://dx.doi.org/10.5772/intechopen.85216*

etc. (**Table 1**) [36, 37].

human disease.

Hyperbaric Medicine.

Hyperbaric Medicine was founded in 1988.

#### **Table 1.** *UHMS- and FDA-approved indications for hyperbaric oxygen therapy.*

effectiveness of HBOT in stroke patients [22].

**74**

**Table 1.**

Air or gas embolism

Decompression sickness

Intracranial abscess

Thermal burns

Exceptional blood loss anemia

Necrotizing soft tissue infections Refractory osteomyelitis

Skin flaps and grafts (compromised)

Carbon monoxide poisoning; cyanide poisoning; smoke inhalation

mizes oxygen content and glucose metabolism in the brain [27].

Crush injuries, compartment syndromes, and other acute traumatic peripheral ischemias

in osteomyelitis [21]. In 1966, Saltzman and coworkers from the USA proved the

In 1970, Boschetty and Cernoch of Czechoslovakia conducted a trial of HBOT for multiple sclerosis. In their series 15 out of 26 patients with multiple sclerosis showed improvement after HBOT at 2 atmospheres [23]. In 1971, Lamm of West Germany used HBOT for treatment of sudden deafness. It was shown that HBOT shortens the course of healing in high-pitch perception dysacusis by upregulating constitutive nitric oxide synthase in the substructure of the cochlea [24]. In 1973, Thurston pioneered studies that showed lower mortality figures in patients with myocardial infarction treated with HBO. HBOT was shown to improve oxygen supply to the threatened heart and reduce the volume of infarct size and other major adverse outcomes [25]. In 1972, Richard A Neubauer set up the Ocean Hyperbaric Neurologic Center in Lauderdale-by-the-Sea exclusively for HBOT in the management of various central nervous system disorders. He mooted the concept of "idling" neurons capable of surviving for years or even decades after the original injury. He claimed that these injured neurons could be re-activated with HBOT and that the greater the number of idling neurons, the better would be the patient's response to HBOT [26]. Neubauer was also the co-founder and executive director of the American College of Hyperbaric Medicine. After his death in 2007 at the age of 83, his clinical research center in Florida was renamed the Neubauer Hyperbaric Neurologic Center. In 1976, Hollbach and Wasserman determined that 1.5 ATA (atmospheres absolute) maxi-

In 1985, RE Marx and his colleagues observed that the rate of osteoradionecrosis was 30%/patient in patients treated with penicillin alone while rates in those treated with HBO was only 5% [28]. In 1987, Jain successfully treated patients with paralytic stroke using HBOT [29, 30]. In 2002, a US Army study confirmed that HBOT repairs white matter damage in children with cerebral palsy. In 2005, Stoller of the USA treated the first case of a child with fetal alcohol syndrome using HBOT and with good outcome [31]. In 2006, Thom of the USA discovered that HBO causes stem cell mobilization [32]. In 2010, Godman discovered that HBOT activated 8101 genes, resulting in reduction of inflammation and increase in growth in body tissues [33, 34]. In 2011, Stoller treated the first retired National Football League (NFL) player for chronic traumatic encephalopathy [35]. In 2012, Harch and his colleagues demonstrated that blast-induced postconcussion syndrome and post-traumatic stress disorders responded to HBOT [15].

Clostridial myositis and myonecrosis (gas gangrene)

Enhancement of healing in selected problem wounds

Delayed radiation injury (soft tissue and bony necrosis)

*UHMS- and FDA-approved indications for hyperbaric oxygen therapy.*

The UHMS and FDA approved HBOT for treatment of conditions like autism, stroke, air embolism, ischemic limbs, split-thickness skin graft acceptance, failed grafts, flap survival and salvage, wound reepithelialization, acute thermal burns, etc. (**Table 1**) [36, 37].

Many patients do not respond to aggressive acid-suppressing medications. HBOT has a beneficial effect in patients with blunt duodenal trauma, duodenal ulcers, and indomethacin-/radiation-induced gastritis. This salubrious effect is mediated by decreased production of oxidative stress markers like tumor necrosis factor-alpha, interleukin-1beta, neopterin, myeloperoxidase, and malondialdehyde. HBOT is seen to improve the acid-neutralizing function of the stomach, normalize gastric motility, reduce the duodenum acidification, decrease edema, and improve the blood flow both in human and equine studies [38, 39]. These effects were also seen in cases of inflammatory bowel diseases like Crohn's [40].
