Notes on Practice: Hyperbaric Oxygen Therapy Used to Treat Radiation Injury: Two Case Reports
Radiation is widely used in medicine, industry, agriculture, and research. Despite improvements in radiation safety, accidents with serious health consequences still occur. The harmful effects of ionizing radiation are well documented.
Radiological accidents due to radioactive substance contamination are rare; local acute reaction to radiation exposure (which can be acute, protracted, or fractioned) is seen more frequently than whole body radiation complications and may occur alone or together with other injury such as trauma or thermal burn. Symptoms observed within a few months following radiation exposure are collectively called acute radiation syndrome. The clinical features and severity of acute radiation syndrome depend on the amount and velocity of the dose, tissue sensitivity, body site, and the width of the affected area. Extremities, especially the hands, are the sites most affected by local radiation injury.1-3
Diagnosis of Acute Radiation Syndrome
Diagnosis of acute radiation syndrome is based on clinical features and laboratory tests. Early diagnosis of radiation injury includes blood count (absolute lymphocyte) and cytogenetic measurement (at least 48 to 72 hours after exposure). Using the cytogenetic method, the minimum dose of radiation exposure that can be detected is 200 mGy for X- and g-ray and 10 to 20 mGy for fission spectrum neutrons.4,5 Chromosomal aberrations may indicate radiation injury but do not provide sufficient information to determine the offending dose.6
Chromosomal aberration analysis takes 3 days because of the 48-hour lymphocyte metaphase period. Lymphocytes are the cells most sensitive to radiation; therefore, the most sensitive and useful laboratory test in the early diagnosis of radiation injury is the absolute lymphocyte count in the blood. A complete blood count must be performed immediately and repeated in 6 hours. A decrease in absolute lymphocyte numbers suggests a recent exposure. If initial white cell and platelet counts on admission are abnormally low, the exposure probably took place a few days to a week earlier. Immunologic disorders occur in the first 48 hours.7
Clinical findings of local radiation injury are erythema, blisters, edema, loss of skin continuity, dry and wet desquamation, open wound, and necrosis. Direct contamination is not uncommon in local radiation injury.8
Medical management of radiation injury depends on the level of emergency. Early clinical signs and symptoms of physical trauma, thermal or chemical burns, and radiation injury determine the classification and manner of first aid. Local injuries require appropriate wound care: the basic principles of treating local injury are moist and frequently changed dressings, debridement of the necrotic areas, and infection avoidance. Amputation is sometimes required.8,9 Local radiation injuries caused by high doses of radiation (>8 to 10 Gy) resemble thermal burns except for delayed (a few days to weeks) signs and symptoms.
Hyperbaric Oxygen Therapy
Hyperbaric oxygen (HBO) therapy is a form of treatment in which a patient breathes 100% oxygen intermittently in a special chamber at 2 to 3 absolute atmospheres (ATA). Hyperbaric oxygen therapy has been used for chronic and delayed radiation injuries for 30 years10 and improves fibroblast growth, collagen formation, neovascularization, epithelialization, and leukocyte bactericidal activity. It also reduces tissue edema. All of these effects are beneficial to wound healing.11
Case 1. Four days after day-long exposure to gamma rays, 26-year-old Mr. A experienced fatigue and weakness and sought the help of the Turkish Atomic Energy Agency. Mr. A was a non-smoker in good health before the accidental radiation exposure. Chromosomal dysenteric aberration analysis was performed on Mr. A and three colleagues to determine the dose of radiation. Lymphocyte numbers, total dysenteric and acentric lymphocyte numbers, and measured radiation doses are shown in Table 1 (data missing for January date).
Eleven days after exposure, Mr. A experienced erythema and a burning sensation on both hands; 17 days after the accident he had blisters. The blisters and necrotic tissue were addressed 25 days after the exposure at the Plastic Surgery Polyclinic of the Cerrahpasa Faculty of Medicine where debridement and wound care with daily moist dressings was administered.12 Forty-two days after exposure, HBO therapy was recommended; 10 sessions were administered at a private hospital over 45 days in irregular fashion. On March 10, 2003 — 3 months after the exposure — Mr. A was admitted to the Undersea and Hyperbaric Medicine Polyclinic of GMMA Haydarpasa Training Hospital with open wounds on his fingers.
Mr. A had lesions on the first, second, third, and fourth distal phalanxes of both hands (see Figure 1a, b) with evidence of necrosis. Hyperbaric oxygen therapy immediately was initiated and continued for 56 sessions at a pressure of 2.4 ATA, 5 days a week, one 120-minute session a day. Necrotic tissue debridement and daily wound care were performed as needed. Antibiotic therapy was determined according to swab culture, which showed coagulase negative Staphylococcus aureus, S. aureus, and Enterococcus faecalis. In response to the results of culture-antibiogram reports, fucidate sodium, levofloxacin, and teicoplanin were used at different times. Despite advice, Mr. A refused radical debridement and surgery.
After a 45-day interval and completion of the first course of HBO therapy, a second 84-session course of HBO therapy was administered. No adverse effects of HBO therapy were observed during the treatment. At the end of the HBO treatment, tissue nourishment improved and necrotic areas cleared. However, contractures developed in the first, second, third, and fourth fingers of the left hand and in all fingers of the right hand (see Figure 2a, b). Mr. A eventually underwent surgical removal of one finger that had a 90-degree contracture.
Case 2. When 24-year-old Mr. B suffered contamination from scattering gamma rays emitted by iridium 192 on September 22, 2003, he went to the Turkish Atomic Energy Agency Cekmece Nuclear Research and Education Center, where chromosomal dysenteric aberration analysis was performed. Mr. B was a healthy non-smoker. Eighteen days after exposure, both of Mr. B’s hands had erythematous lesions (see Table 2); 21 days after exposure, HBO treatment was started. Lesions were noted on the distal phalanx of the first finger, the entire palmar face of the second finger of the right hand, and the distal phalanx of the first finger of the left hand (see Figure 3a).
Hyperbaric oxygen therapy treatment was performed 5 days a week at 2.4 absolute atmospheres for 120 minutes. No side effects were observed during or after HBO therapy. The blisters that occurred after a few days of HBO treatment were opened and cleared by surgical techniques (see Figure 3b). After 15 sessions of HBO treatment, all the wounds were healed and HBO treatment was stopped (see Figure 4). Movement of the fingers, restricted before HBO therapy, improved.
Although the pathophysiology of delayed radiation injuries is still obscure, the consistent findings of endarteritis and tissue hypoxia contribute to its pathogenesis.9,13 The source of free radicals due to radiation injury is water.1,14 Water transforms to H+ and OH- ions in the radiation environment. This process is independent of the free oxygen presence in the environment. In addition, the structure and function of the DNA and other biologic molecules are changed by free radiation energy.14
Hypovascular, hypoxic, and hypocellular — the so called “3 H tissue” — is the end result of delayed radiation injuries. These may manifest as bony or soft tissue injuries in different anatomic sites, depending on the irradiated area.
Marx et al15 showed a dose-dependent increase in vascular density in irradiated rabbits treated with HBO. Feldmeier et al16,17 provided evidence of diminished fibrosis in the pelvic and abdominal organs of mice receiving whole abdominal irradiation and then receiving post-irradiation HBO compared to those receiving the same radiation course without HBO. Quantitative morphometry, determining and contrasting the relative percentages of collagenous versus non-collagenous components in small and large bowel and kidney in these animals, confirmed the reduction of tissue fibrosis in animals receiving HBO 7 weeks after radiation exposure.16
The efficacy of HBO therapy in the cases presented here could not be fully clarified due to the absence of a control group. In the first case, the patient was re-admitted to the authors’ center when the existing wounds on both hands worsened and infection progressed post HBO therapy interruption. When HBO therapy resumed, infection was reduced and the wounds closed.
Infection developed in the radiation-damaged region because of impaired local tissue circulation which, in turn, impaired healing of the skin lesions that formed under the effect of 3 H tissue. By stabilizing oxygenation in these tissues, HBO therapy helped reduce infection and, because of increased vascularization, accelerated wound healing. In the second case report, radiation-induced hypoxic ischemic tissue formation was restricted with HBO therapy (the radiation exposure in Case 2 was approximately 66% of that in Case 1).
To the authors’ knowledge, the use of HBO for the acute phase of radiation injury has not been recommended to date. This may be due to fear of increasing free oxygen radicals.18 It has been shown that free oxygen radicals increase in a hyperoxic environment.19 However, the human organism has the ability to scavenge free oxygen compounds. The use of both glutathione and the antioxidant vitamin E, and of vitamin E in combination with vitamin C, potentiates this ability.20-22 In their study, Dennog et al23 detected significant oxidative DNA damage immediately after HBO treatment; 24 hours later, no DNA damage was found. In addition, HBO caused oxidative DNA damage only after the first treatment and not after further treatments under the same conditions, indicating an increase in antioxidant defenses.
Further, xantine oxydase becomes active in the hypoxic environment and is responsible for free radical formation, as well as for increased oxygen radicals seen in the hypoxic phase of reperfusion injury.24 Because endarteritis and hypoxia play an important role in the ethiopathology of radiation injury, HBO therapy probably contributes to combating acute radiation injury — HBO attenuates oxygen radical formation by preventing tissue hypoxia. This would appear to account for the good outcome in Case 2, in which HBOT was started early in the clinical course of acute radiation injury.
The same treatment principles apply in acute radiation injury as in burn injuries in skin lesions.1 Providing moist and frequent dressing changes, debriding the necrotic area, and avoiding infection are needed to improve the lesions. Hyperbaric oxygen therapy enhances the effects of these treatment measures. Hence, HBO therapy may be used in the treatment of accidental local radiation injury.
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2. Planning the Medical Response to Radiological Accidents. International Atomic Energy Agency, Safety Report Series No. 4, I.A.E.A. Vienna, Austria;1998. Available at: http://www-pub.iaea.org/MTCD/publications/PDF/Pub1055_web.pdf.
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