Title: MEDICAL MANAGEMENT OF RADIOLOGICAL CASUALTIESVersion 1.

Prepared by:

Dr. Eduardo D. Herrera Reyes. Medical Emergency Preparedness Specialist. Incident and Emergency Centre.Mail : E.D.Herrera-Reyes@iaea.org T: (+43-1) 2600-21408

Modified by

Dr. Kenzo Fujimoto

E-Mail: kenzo-fujimoto@jcom.home.ne.jp

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4.1 History of Radiation injuryIntroduction

4.2 Mechanism of radiation injury

4.3 Maximum tolerant dose of normal tissue to therapeutic irradiation

4.42 Basis of medical management on radiation injury

4.5 Methods of triage for treatment

4. 63 Decontamination of skin and hair

4.74 Management for contaminated skin injury

4.85 Management for internally deposited radionuclides

4.96 Diagnosis and medical management of radiation syndromes

4.107 Psychological support

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MEDICAL MANAGEMENT OF RADIOLOGICAL CASUALTIES

4.1 History of Radiation injuryIntroduction

This chapter is not written for medical staff but for the emergency workers to understand and to relieve anxiety for the medical treatment in case of high exposure or intense contamination. Therefore, most parts of the content is described briefly.

First priority of handling victims is to stabilize their physical condition even if they are contaminated or exposed by radiation. Radiation effects are not the matter of first priority except the internal contamination due to plutonium. Radiation exposed or contaminated persons can be dealt with radiological problems after the urgent conventional medical treatment. Even the highly exposed victims have time before manifesting illness due to exposure after prodromal syndrome. During that time after the exposure which is at least for two days even in case of severe exposure it is necessary to estimate the exposed dose for the prognosis and future treatment.

Discovery of Ionizing Radiation

In 1895 Wilhelm Roentgen announced the discovery of “a new kind of ray” with previously unknown properties that could penetrate the human body and reveal broken bones. Roentgen assigned the letter “X” to represent the unknown nature of the ray and thus the term X ray was born. The first radiograph was made in January 1896 and Roentgen received Nobel Prize in Physics in 1901.

Antoine Becquerel discovered the natural radioactivity of uranium (1896), for which he shared the 1903 Nobel Prize for physics with Marie and Pierre Curie.

First Reports on Harmful Effects

Less than a year after the discovery of X rays in 1895, cases of radiation induced alopecia and dermatitis were reported. However, as can be seen from the lack of shielding of the X ray tube in the picture of an early X ray examination, the dangers of prolonged X ray exposure was not fully appreciated. In 1901, the first harmful effect of radioactivity was reported: a nasty skin burn was attributed to the vial of radium, which Becquerel carried in his vest pocket. The first radiation induced skin cancer was reported in 1902. The first radiation induced leukaemia was described in 1911.

The first recorded biological effect of radiation was due to Becquerel, who inadvertently left a radium container in his vest pocket. He subsequently described the skin erythema that appeared two weeks later and the ulceration that developed and required several weeks to heal. It is said that Pierre Curie repeated this experience in 1901 by deliberately producing a radium “burn” on his own forearm.

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Figure X. Based on Becquerel’s earlier observation, Pierre Curie is said to have used a radium tube to produce a radiation ulcer on his arm. He charted its appearance and subsequent healing.Early radiation workers (working in the first decades of the 20th century) had a higher mortality of leukaemia and higher incidence of skin cancer. Even today, radiation therapy carries with it an increased risk of skin and other second cancers as a result of the therapy. In the 1920s, bone cancer was linked with ingestion of large quantities of radium by women who painted dials on watches and clocks with radium laden paints. The type of bone cancer (oestrogenic sarcoma) is rare, however it occurred with alarming incidence in radium-dial painters and its location (primarily in the mandible) is an extremely unusual location for this type of cancer.

In the 1930s, Thorotrast, a colloid solution of radioactive thorium dioxide, was commonly used as a diagnostic contrast agent for cerebral angiography. Thorotrast (a long lived alpha emitter) remains in the body, accumulates in the liver and resulted in liver cancer. Radiation has also been used in the past to treat benign medical conditions with unfortunate consequences such as the increase in leukaemia in children who were irradiated to reduce the size of the thymus gland.

The studies of cancer incidence in Japanese atomic bomb survivors began in 1950, and have formed the basis of radiation protection guidelines ever since. Five cancer sites/types (leukaemia, colon cancer, lung cancer, stomach cancer and breast cancer) have been identified in survivors of atomic bombing in Hiroshima and Nagasaki. The health impacts to survivors is studied by the Radiation Effects Research Foundation (RERF in Hiroshima) and serves as a unique resource to the radiation biology and regulatory community who are responsible for estimating the cancer and other risks of radiation exposure in humans. Approximately 43% of the survivors are still alive and radiation induced cancer risk data continue to be re-evaluated. The first reports of excess leukaemia among radiologists appeared in the 1940s and excess cancer attributable to medical radiation were reported in analytical studies in the 1950s.

The population of children living around Chernobyl manifest a ten- to thirty-fold increase of thyroid cancer in Belarus, the northern regions of Ukraine and in two western districts of Russia in the 1990s. Some of the other populations studied and their associated cancers include: lung cancer in uranium miners and breast and other second cancers in radiation therapy patients.

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4.2 Mechanism of radiation injury

One of the first theories to explain how ionizing radiation could damage the cell is the “target theory”: once specific targets within the cells were hit by radiation, this would cause cell death.

Explanations of the biological action of X rays fall into two main categories, which for convenience of reference we may label the “poison” hypothesis and the “target” hypothesis. The poison hypothesis postulates that the radiation produces, by photochemical action on the substance of the nucleus, a certain concentration of some unspecified poisonous material which, by diffusion to the structures concerned, results in the changes which are actually observed. The target hypothesis focuses attention on the discontinuous nature of X ray absorption, and assumes that action takes place whenever one of the biological structures is “hit” by the radiation... My own suggestion... is that a “hit” is registered when a pair of ions is produced anywhere within the sensitive particle" (Crowther, 1938). In the light of the data available, Crowther rejected the "poison" hypothesis, since only the "target" hypothesis could be reconciled with all the experimental facts. During the intervening ten years the subject of radiobiology has made rapid progress and a considerable body of experimental evidence has been accumulated. In the hands notably of the late Dr. D. E. Lea and his collaborators, the target "hypothesis" has become the target "theory", elaborated very clearly in his book, Actions of Radiations on Living Cells (Cambridge University Press, 1946).

Linear energy transfer, Absorbed dose and Relative Biologic Effectiveness

Linear energy transfer (LET) is the energy transferred per unit length of the track. The special unit usually used for this quantity is kiloelectron volt per micrometer (keV/μm) of unit density material. In general, alpha particles, have a much higher LET than beta particles or gamma rays.

The relative biological effectiveness (RBE) of high LET radiations is in general much higher than those of low LET radiations with the same energy.

Alpha particles are a high LET radiation

Beta particles and gamma rays are a Low LET radiation

The amount or quantity of radiation is expressed in terms of the absorbed dose, a physical quantity with the unit of gray. Absorbed dose is a measure of the energy absorbed per unit mass of tissue. Equal doses of different types of radiation do not produce equal biological effects. For example, 1 Gy of neutrons produces a greater biologic effect than 1 Gy of X rays. The key to the difference lies in the pattern of energy deposition at the microscopic level.

In comparing different radiations, it is customary to use X rays as the standard. The National Bureau of Standards, in 1954 defined relative biologic effectiveness (RBE) as follows: The RBE of some test radiation (r) compared with X rays is defined by the ratio D250/Dr, where D250 and Dr are, respectively, the doses of 250 kVp X rays and the test radiation required for equal biological effect.

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Figure XXXX. It is shows the RBE for different types of radiation and their effects.

The biological effectiveness of different types of radiation can be characterized by a parameter known as the relative biological effectiveness (RBE). The RBE is defined as the ratio of the dose of a standard type of radiation to that of the test radiation that gives the same physiological effect. The standard type of radiation was usually taken as 200 or 250 kVp X rays, but now Cobalt-60 gamma-ray energies are used mainly as the standard for comparison.

The RBE of high LET radiations compared with that of low LET radiations increases as the dose rate decreases. RBE varies according to the tissue. In general, RBE values are high for cells or tissues that accumulate and repair a great deal of sublethal damage, so that their dose-response curves for X rays have a broad initial shoulder.

RBE depends on the following: Radiation quality (LET); radiation dose; dose rate; biologic system; biological effect.

The relative biological effectiveness of radiation for producing stochastic effects (cell mutation) is higher than for producing deterministic health effects (cell death).

Radiation interactions that produce biological changes are classified as either direct or indirect. The change takes place by direct action if a biological macromolecule such as DNA, RNA, or protein becomes directly ionized or excited by an ionizing particle or photon passing through or near it.

Figure XX. The direct action of ionizing radiation on DNA is the main mechanism for high LET radiations

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Figure XXX. The indirect action of ionizing radiation on DNA is the main mechanism for low LET radiations

Indirect effects are the result of radiation interaction within the medium (e.g., cytoplasm) creating reactive chemical species called free radicals that in turn interact with the target molecule. Because 70–85% of the mass of living systems is composed of water, the vast majority of low LET radiation induced damage is mediated through indirect action on water molecules. The water molecule absorbs energy and disassociates into two radicals with unpaired electrons in the valance shell. These are denoted by the symbols H• and OH• below

H2O → H+ + OH- (ionization)

H2O → H•+OH• (free radicals)

Free radicals are extremely reactive chemical species that can undergo a variety of chemical reactions. Free radicals can combine with other free radicals to form non-reactive chemical species such as water in which case no biological damage occurs, or with each other to form other molecules, such as hydrogen peroxide, which are highly toxic to the cell. Although their lifetimes are limited (<10–5 sec), free radicals can diffuse in the cell producing damage at locations remote from their origin. Free radicals may inactivate cellular mechanisms directly or via damage to genetic material (DNA and RNA) and are believed to be the primary cause of biological damage from low LET radiation.

Carcinogenesis induced by radiation

Cancer arises from abnormal cell division. Cells in a tumour are believed to descend from a common ancestral cell that at some point loses its control over normal reproduction (typically decades before a tumour results in clinically noticeable symptoms). The malignant transformation of such a cell comes about through the accumulation of mutations in specific classes of genes. Mutations in these genes are a critical step in the development of cancer.

Radiation dose from external radiation sources as well as internally deposited radioactivity have been shown to lead to increased rates of cancer induction in animal experiments and in human populations. High radiation doses have been linked to a modest increase in the incidence of cancer in exposed populations, such as the atom bomb survivors in Japan. The observed effect is dose-dependent. However, the dose-effect relationship described in animal experiments cannot be directly adopted/extrapolated to human population. At low doses, below about 100 mSv, the

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potential for cancer causation is uncertain and generally believed to be quite small. Extrapolation of the risk down to zero excess doses is commonly accepted as a reasonably conservative convention for radiation protection and safety purposes.

Ionizing radiation is just one of them and is a weak carcinogen at low dose levels. Ionizing radiation is a relatively weak carcinogen, thus it is associated with occupational and medical exposure, the increased risk is considerably small compared to the background incidence of cancer and genetic effects in the population at large. According to the SEER ((Surveillance, Epidemiology and End Results) Program of the National Cancer Institute (in the USA)), the natural incidence of cancer in the population of the USA, over a lifetime, is estimated to be approximately 44% and the risk of mortality is approximately 22%. In addition, radiation does not produce any unique type of cancer, nor is the latency or pathology of a particular cancer different from cancer from other aetiologies. Experiments in animals and cells provide insight into the variables of radiation induced biological effects; however, they suffer from the limitation that they do not represent human response to radiation. Stochastic effects of radiation in humans can be detected by epidemiological-statistical methods in large population groups.

There is no method available to prove that any cancer of a radiation worker is from the radiation dose received. The real cause may be of non-radiological nature. Nevertheless, there are scientific aids available to calculate the degree of probability of cancer induction by radiation exposure. Even in this case, the calculated value shows only the probability of radiation aetiology but does not prove it.

Unlike genetic effects of radiation, radiation induced cancer is well documented. Many studies have been accomplished which directly link the induction of cancer and exposure to radiation.

One additional caseduring whole life for 100 persons, each exposed to 100 mSv (in addition to natural background). 42 other cases will be detected induced by other different causes, non radiation related (BEIR VII Report 2005 – Low LET Radiation).

4.3 Maximum tolerant dose of normal tissue to therapeutic irradiation

This point needs to be clarified. Why therapeutic irradiation? To which tissue, please futher clarification to complete.

4.42 Basis of medical management on radiation injury

Until the arrival of Emergency Medical Response Team on the scene, First Responders (Facility Responder, police, fire service, or other personnel who have been adequately trained in techniques of basic first aid) can provide emergency first aid for injured person(s).

Radiation exposure or contamination with radioactive material does not cause immediate signs or symptoms and, therefore, if victims are unconscious, disoriented, burned, or otherwise in distress, look for causes other than radiation.

Some

For deterministic effects, the radiation symptoms or signs can be modified by some treatments after irradiation. For stochastic effects on the contrary, there are no treatment to change the occurrence

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probability of the effects. Accordingly, deterministic effects needs to be diagnosed or predicted and treatments to reduce the damages should be considered. For stochastic effects namely cancer, medical follow-up may detect cancer in early stage and be able to reduce negative impacts of radiation. Thus, proper follow-up program should be implemented for each victim depending on dose.

In case of contamination, radiation exposure continues while the radioactive materials exist on the body surface or in the body. Thus, early decontamination can reduce the radiation dose to the body. This principle is true both for surface contamination and internal contamination.

4.5 Methods of triage for treatment

The health status of the patient is the main consideration in all the radiation emergencies. Unstable patient and Life-threating conditions are priorities. Medical triage should be conducted based on traditional surgical and medical considerations. Once the individual is medically stable, radiological dose magnitude estimation and treatment planning to be address the ramifications of the anticipated dose can begin.

Some important factors to consider in the triage are the following:

[(i)] Number of victims.[(ii)] Each victim's medical status and type of injury.[(iii)] If victims have been surveyed for contamination.[(iv)] Radiological status of victims (exposed vs. contaminated).[(v)] Identity of contaminant, if known.

In major accidents such as the Chernobyl accident, the decision on the need for treatment and prognosis of the individual accident victim cannot be based on dose estimates which are time consuming, uncertain and with little impact on the medical response. Rather, these decisions have to be based on clinical criteria which are simple, early and permit the reliable identification of accident victims who do not need special treatment. It is more important not to miss any victim who may need treatment than to identify only those who will certainly need treatment. Such criteria have been established for many decades and they proved their usefulness particularly in the acute aftermath of the Chernobyl accident, when the members of the rescue teams had to be assessed as to who would need which treatment and when.

In order to prepare an effective treatment plan, an estimation of the dose magnitude is needed.

4.63 Decontamination of skin and hair

The first priority is to ensure the patient is medically stable.

After the medical stabilization of the patient is achieved then the screening is carried out to find the contamination by radionuclides. If the contamination is found it is better to be removed as soon as possible and as much as possible. Later, firstFirst step for the decontamination is clothing removal of

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clothes. It stands to reason that clothing typically covers large percentage part of the body, by thentherefore properly removing the clothing will likely significantly decrease the amount of radioactive material from the body surface with which the healthcare provider has to contend. This is done by cutting, not tearing, the clothing in a direction away from the patient’s airway and rolling it outward away from the patient’s skin, trapping the material in the clothing.

Ehen decontaminating the skin, care should be taken to avoid visible irritation. Abrading the skin may allow an entry point for radioactive material.Skin contamination is wiped or rinsed with water. Wiping or rinsing can be repeated several times until the measurement indicates that the procedures would not noticeably decrease the contamination any more. During these procedures, the operators should exercise caution not to create a skin scratch nor an abrasion. These skin damages could lead to internal contamination, which is worse than radioactive materials on the skin.

Should hair become contaminated it can be washed, taking care not to allow the wash/rinse water to run to the face. Clipping the hair is a better idea, but only if necessary. Do not shave or clip the eyebrows. Contaminated hair needs to be wiped or washed with water. If decontamination of hair with washing is not effective enough, hair cut can be an option on the condition that the consent of the patient would be obtained. When hair wash is performed, it is important to avoid drainage water to be splashed around the mouth, the nose, or the eyes.

4.74 Management for contaminated skin injury

Once clinical condition of the patient has been stabilised, the next priority is to treat wounds that might be contaminated. Wound dressings should be removed and saved for further evaluation. After irrigating the wound gently with sterile saline, adequate equipment with a probe should be used to evaluate the effectiveness of the decontamination process. The intact skin immediately adjacent to the wound must be quickly decontaminated, and drapes should be applied in the area to prevent spread of radioactive materials. The wound dressing should be removed and saved for further evaluation. The intact skin immediately adjacent to the wound should be quickly decontaminated using a wipe.

After the draping is properly applied, wound decontamination can begin. Gently irrigate the wound using sterile saline or something similar. The purpose of the initial irrigation is to attempt to remove the bulk of the contamination, so do not be too aggressive in order to prevent splashing and potentially spreading contamination. The run-off should be directed into a receptacle. All waste generated should be kept in a pre-arranged location for later collection and disposal.

If the wound is still contaminated, the process should be repeated until no further progress is overly slow or no existing, the wound should be explored for foreign bodies by treating physician.Most of radionuclides are not absorbed through a normal skin, with an exception of tritium. However radionuclides can be absorbed through injured parts, or wounds. Thus, radionuclides in wounds need to be removed as soon as and as much as possible to reduce internal contamination. Regular procedure of the wound decontamination is irrigation with normal saline solution or water. The irrigation can be repeated several times until the measurement results show no significant decrease anymore. After irrigation, treat the wound like wounds without contamination.

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4.85 Management for internally deposited radionuclides

The health status of the patient is the main consideration before to manage any internal deposited radionuclides. The management of life-threatening conditions must have absolute priority and handled under traditional medical and surgical protocols. Dose estimations, decontamination procedures and decorporation therapy are secondary priorities in these cases.

Health risks for professionals handling an unstable and contaminated patient with radionuclides are practically negligible, considering the potential very low radiation exposure, and the use of protective clothes and adherence to universal bio-safety standards.

Metabolism and elimination kinetics of the non-radioactive analog determine the metabolic pathway of the radionuclide. The major routes of incorporation are inhalation, ingestion, absorption through an open wound contamination, and transdermal absorption.

When an internal and/or external contamination is suspected, the following steps will provide important information for the treatment:

A quick head-to-toe radiological survey should be performed by a radiation protection officer (or otherwise by a trained individual) with appropriate equipment, including a judicious survey of wounds. This should provide sufficient evidence of the presence or absence of gross contamination.

Nasal (from each nostril separately) and oral swabs should be obtained, and samples from wounds and under the fingernails also collected. All samples must be kept and labelled properly, including patient’s name and day and hour of the sample collection. Samples must be sent to radiological measurement.

Besides specific in-vivo and in-vitro dosimetry procedures for the definitive diagnosis of internal contamination, any patient with a history of internal contamination should also be submitted to specialized medical centre and evaluated to assess the clinical condition and to rule-out whole-body external exposure.

Generic procedure for decorporation of internally deposited radionuclides is shown in the generic procedures for medical response during a nuclear or radiological emergency in EPR-MEDICAL [201]. Main aspects of the procedure are shown below.

Identification of radionuclides and rough dose assessment of the internal contamination is desirable to be obtained before starting treatment for internal contamination. At least one of the following tests will be conducted for that purpose when there is possibility of internal contamination:

Nose smear test; Body surface contamination screening, especially wounds screening; Measurements by a whole body counter.

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When the above mentioned tests could not indicate, but internal contamination is still suspected, it is necessary then to carry out bBio-analyses for the identification and quantification of radionuclides in the body (with urine, faeces and blood samples) . While, they are a time consuming procedure (24 to 48 h), so that there may be instances when the physician must decide whether or not to begin treatment exclusively on the basis of presumptive evidences. Some clinical decisions to initiate or not treatmentto, even without the confirmatory tests at hand, are based on the following:

History Character of the accident, strength of circumstances and results of estimations; Radioactive concentration in the air where the workers was present; Probable pathway of contamination (worst scenario: through wounds); Solubility of the contaminant radioactive material (if known); Radiotoxicity of the contaminant (if known); Patient’s age and his/her specific clinical conditions; Toxicity of the drug to be used for decorporation.

The medical treatment of internal contamination will include at least one of the following aspects:

Reduction / inhibition of absorption of the isotope in the gastrointestinal tract. Blocking uptake to the organ of interest. Isotopic dilution. Altering the chemistry of the substance. Displacing the isotopes from receptors. Traditional chelation techniques. Early excision of radionuclides from wounds to minimize absorption. Bronchoalveolar lavage in some cases.

Decorporation of internal contamination is not an easy task. It is better to decide based on estimated dose if possible, efficiency of decorporation and adverse effect of each treatment. And there are only limited decorporation agents which could apply to certain radionuclides.

4.96 Diagnosis and medical management of radiation syndromes

Cutaneous radiation syndrome (CRS)

The skin is a complex tissue and the cutaneous radiation syndrome (CRS) refers to a number of pathologies that may become manifest after exposure of the skin to ionizing radiation.

The skin has three layers, epidermis, dermis and hypodermis. The target cell population, damage to which causes denudation of the epidermis, is the basal cells of the epidermis, including those cells situated within the canal of hair follicles.

The epidermis is the outer layer of the skin. The majority of cells in the epidermis are keratinocytes. Epidermis is a hierarchical tissue. This classical hierarchical organization of the epidermis explains its typical acute response following exposure to ionizing radiation.

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The dermis is a layer of skin between the epidermis and hypodermis, and is composed of two layers, the papillary and reticular dermis. Structural components of the dermis are collagen, elastic fibres, and extrafibrillar matrix.

The hypodermis, also called the hypoderm, subcutaneous tissue, or superficial fascia is the lowermost layer of the integumentary system in vertebrates. Types of cells that are found in the hypodermis are fibroblasts, adipose cells, and macrophages. It is derived from the mesoderm, but unlike the dermis, it is not derived from the dermatome region of the mesoderm.

The dermis and hypodermis are flexible tissues that mainly develop late effects after radiation exposure.

The latent period for the manifestation of a specific pathology is dependent on the characteristics of the target cells responsible for the development of that lesion and the dose of radiation delivered to those target cells. The intensity and duration of the lesions are also dose dependent. Since the depth dose distribution of a radiation source is dependent on the radiation quality, the development of a specific lesion, its intensity and its duration will also vary with radiation quality. The CS may appear as an isolated lesion or as a number of lesions occurring simultaneously or over different time scales. In dealing with the cutaneous tissues the concept of dose is meaningless unless it is associated with a reference depth dose distribution to indicate the level of injury to specific target cells.

Especially for non-uniform irradiation, skin injury becomes main concern in some cases. Table A indicates dose and time to cause some skin symptoms.

Table A

Stage/symptoms Dose range (Gy) Time of onset (d)

Erythema 3–10 14–21

Epilation >3 14–18

Dry desquamation 8–12 25–30

Moist desquamation 15–20 20–28

Blister formation 15–25 15–25

Ulceration (within skin) >20 14–21

Necrosis (deeper penetration)

>25 >21

[201, 202]

Local radiation injury results in skin lesions quite similar to thermal burns. However, thermal burns are different from “radiation burns” in the following aspects:

Radiological burns are dynamic; their temporal and spatial evolution is unpredictable and even relatively independent of the initial clinical evolution;

Patients do not present initial shock;

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Pain is not immediate in local radiation injury, but when it later appears it is very severe and resistant to drugs;

It is a prognostic symptom which heralds indicates a new wave of clinical recurrence;

Although the kinetics of radiation burns are highly dependent on the local absorbed dose, they usually exhibit an early (primary) erythema without tissue nor hair loss at the beginning (however, they may occur two weeks after exposure), while thermal burns involve early hair and tissue loss (depending on the depth of the burn).

After an acute irradiation, high dose-rate will include the following clinical manifestations:

8–12 Gy*: Erythema, dry desquamation, skin pigmentation.

12–30 Gy*: Erythema, oedema, blistering, moist desquamation, atrophy of skin, subcutaneous layer and muscles, later radiation ulceration.

30–50 Gy*: Erythema, oedema, blistering, erosions, deep ulcers, deep trophic, degenerative and sclerotic changes, initial necrosis.

> 50 Gy*: Erythema, oedema, local haemorrhages, necrosis, effects of amputation, ulcer relapses, contractures.

Figure XXXX. It shows the evolution of a radiological burn in an industrial gammagraphy accident. The patient received a high radiation dose that required the amputation of one leg. The figure it shows the evolution in first 18 days post irradiation (PI). The CRS is a dynamic process, in which the lesion cans extent in surface and in depth. Recurrences several years after the irradiation are also expected in the evolution of these patients. From: The Radiological Accident in Yanango, IAEA, 2000

Late effects of local radiation injury depend upon the degree of severity in the early stages, and the late effects can vary from slight skin atrophy to constant ulcer recurrence and deformity. In the late period, there may be atrophy of the skin and epidermis as well as occlusion of small vessels with subsequent disturbances in the blood supply, destruction of the lymphatic network, regional lymphostasis, and increasing fibrosis and sclerosis of the connective tissue.

The treatment in these cases will depends on the severity of the absorbed doses. The management of these patients is oriented to establish dose estimations of the lesions at early stage. Different methods are available, which include: biological dosimetry (limited information in partial irradiation),

*RBE weighted dose

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dose reconstruction by physical and software methods. According to doses estimations, the treatment will range since local symptomatic treatments (creams and topics treatment) to very complex therapies including dosimetrical guided surgery and mesenchymal stem cells injections.

Acute Radiation Syndrome

A combination of clinical signs and symptoms are occurring in stagesphased over a period of hours to weeks due to a significant partial-body or whole body exposure of > 1 Gy, as injury to various tissues and organs is expressed.

ARS has 4 phases: (1) prodromal phase, (2) latent phase, (3) manifest illness, (4) death or recovery.

As a part of diagnosis, exposed dose should be identified. Exposed dose can be assessed by biological methods or physical methods. Some typical methods for external exposure are listed in Table B. As one of biological methods, clinical symptoms are very useful for dose estimation although it is applicable only for high dose. Prodromal symptoms, such as nausea, vomiting, or diarrhea have threshold. Latency periods and degree of symptoms are depending on dose, so the existence and degree of symptoms are useful information. Lymphocyte count is also a useful tool for dose estimation, because lymphocyte count starts to decrease quite rapidly just after a few hours. Chromosome analysis is another special method for dose evaluation. However, this method requires at lease two days to obtain the estimates.

Table B. Dose assessment method for external exposure

Category Biological methods Physical methodsTypical methods Clinical symptoms

Lymphocyte count Chromosome analysis

Reconstruction Work environment

assessment Personal dosimeter

Treatments of prodromal syndrome are all symptomatic treatments. In manifest illness period, the treatments are oriented for each organ system, for example, isolation, prophylactic antibiotics, cytokines, blood transfusion, or bone marrow transplantation that can be considered for a bone marrow injury.ARS follows a similar clinical pattern that can be divided into three phases: (1) an initial or prodromal phase occurring during the first few hours after exposure, (2) a latent phase, which becomes shorter with increasing dose; and (3) a manifest phase of clinical illness. The time of onset and degree of the transient incapacitation of the initial phase, the duration of the latent period, as well as the time of onset and severity of the clinical phase and ultimate outcome are all, to a variable extent, dependent upon total dose and individual radiation sensitivity. As a rule, the higher the dose, the time of onset of all three phases and their duration shortens while the prodrome and the manifest illness phase become more severe. The last stage (4) is it the death or recovery of health conditions.

Cytogenetic injury to bone marrow cells and nucleated blood cells can occur at ionizing radiation doses as low as 0.25 Gy, but clinical depression of cell counts is usually not noted until a dose of 0.5 Gy.

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The signs and symptoms of radiation sickness after an acute total body exposure are predominantly the consequences of radiation injury to the haemopoietic tissues in the bone marrow. Proliferating cells of the bone marrow decrease their proliferative activity after radiation exposure. Consequently, fewer cells are available for differentiation and maturation to white blood cells, red blood cells and platelets. Thus, the balance of cell production in the bone marrow and cell elimination from the peripheral blood is disturbed. Yet, mature cells of the myeloid line are not damaged by radiation exposures of a few Gy.

Three different radiation syndromes were associated with these three categories based on the latency to death: the haemopoietic syndrome after doses < 12 Gy, the gastrointestinal syndrome after doses of 12 to 30 Gy, and the cerebrovascular syndrome after even higher doses. The different latencies of the haemopoietic and the gastrointestinal syndrome were explained by the different cell turnover rates of the critical cell lineages in the tissues in which severe lethal hypoplasia occurred lead to death of the animal, i.e. the granulocyte cell production lineage in the bone marrow and the epithelial mucosal cell lineage in the small bowel. Death in the haemopoietic or bone marrow syndrome was associated with septic infection due to agranulocytosis, death in the gastrointestinal syndrome was associated with complete denudation of the small bowel surface leading to profuse diarrhoea and hypovolumic shock.

ARS Haematological type:

Signs and symptoms of the haematopoietic syndrome are directly related to reduction of concentration of specific cells types in the blood. Radiation-induced cytopenia is strongly related to dose. The impact of acute radiation exposure on the physiology of normal haematopoiesis and the balance of cell production in the bone marrow and cell loss after the bcell lineage specific life span has been thoroughly investigated after exposure in humans and animals. Radiation does not decrease life span or function of blood cells but it blocks in a dose dependent way the production of new cells.

Diagnosis, treatment and prognosis will depends on the dose absorbed of the patient. Therapeutics options include expecting the spontaneous recovery; stimulation of haematopoiesis with growth Factors; platelet transfusions; granulocyte colony stimulating factor (G-CSF); intravenous injection of thrombopoietin and the stem cell transplantation or even umbilical cord blood stem cells.

ARS Gastrointestinal type:

Symptoms in the manifest gastrointestinal syndrome, which usually starts in the second week after radiation exposure, are mainly abdominal cramps and diarrhoea. After high radiation doses, the loss of the mucosal covering of the bowels, which if associated with thrombocytopenia, may also lead to bloody diarrhoea and to entry of enteric pathogenic and non-pathogenic bacteria. Since cell turnover is fastest in the small bowel, the signs and symptoms of radiation damage occur earlier in the small bowel than in the large bowel.

The treatment is purely symptomatic with the main emphasis on fluid and electrolyte replacement, systemic antibiotics and analgesics.

ARS Neurovascular type:

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Although electrophysiological studies after total body irradiation with doses >6Gy have demonstrated significant changes at the synaptic level in brain tissue consistent with a state of increased brain excitability, the clinical symptoms are most likely linked to cerebral oedema with an increase in intracranial pressure. Along with early oedema, acute inflammatory reactions occur as well as decrease of the blood-brain barrier. The onset and duration of the different phases of the neurovascular syndrome depend on radiation dose. Symptoms such as nausea, vomiting and anorexia characterise the prodromal phase.

According to the absorbed dose > 50 Gy (gamma radiation) some of the following clinical manifestation has been described: permanent incapacitation syndrome; disorientation; confusion; prostration; ataxia; seizures; absence of deep tendon and corneal reflexes; hyperthermia; respiratory distress; cardiovascular shock; the death commonly occurs in a period between 2 to 3 days.

Hospitalization of these patients is obligatory, medical management has to include intravenous glucocorticoids, electrolyte and fluid replacement and analgesics. Recovery is unlikely and mostly primary symptoms continue intermittently. Only sufficient fluid and electrolyte replacement, analgesic medication and the application of intravenous glucocorticoids and mannitol infusion to reduce intracranial pressure, will increase the patient´s chance of survival.

Figure XXXXX. This figure illustrate the potential health consequences in overexposure and internal/external contamination by radionuclides (ARS: Acute Radiation Syndrome. CRS: Cutaneous radiation syndrome)

4.107 Psychological support

When carrying on medical treatment of exposed or contaminated victims medical staff as well as some relevant persons who come to contact with the patients should always consider psychological aspects of the patients as well as their family members. Most of the cases psychological aspects are more important than the actual exposure or contamination. The medical status and plan for diagnosis and treatment should be explained to the patients as well as to the family. It is necessary to involve the patient in decisions about care. A communication to the family should be allowed as

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much as possible. And psychiatrist or psychologist should be involved in addition to medical treatment.

Radiation symptoms in just a few people can produce devastating psychological effects on an entire community or group of responders as well. The acute anxiety has the potential to become the significant source of emotional stress.

It is clearly recognized that knowledge of radiation and its effects can reduce stress. While the ‘stressor’ or the causative agent cannot be removed, effort is needed to change the way in which it is perceived. Psychological reactions to radiation could be prevented, decreased or relaxed using different methods applied before, during or after the emergency or malicious act. In general, a malicious act involving radioactive material will generate more psychological distress than other types of radiation emergency. Appropriate officials at the national and local levels need to perform the actions needed to arrange psychological support. These actions are to be planned at the stage of preparedness.

References

[201] INTERNATIONAL ATOMIC ENERGY AGENCY, Generic procedures for medical response during a nuclear or radiological emergency, EPR-MEDICAL, IAEA, Vienna (2005).

[202] INTERNATIONAL ATOMIC ENERGY AGENCY, IAEA Safety Reports Series No.2: Diagnosis and Treatment of Radiation Injuries, IAEA, Vienna (1998).

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