Terror attacks using nuclear or radiation-related devices are an unequivocal threat in the twenty-first century and are capable of having unique medical and psychological effects. This chapter will focus on the most probable scenarios of possible attacks and the medical principles of handling such threats.
There are two major categories of potential terrorist incidents with widespread radiologic consequences. The first is the use of radiologic dispersal devices. This could cause a purposeful dissemination of radioactive material without nuclear detonation by using conventional explosives with radionuclides, attacking fixed nuclear facilities, or attacking nuclear-powered surface vessels or submarines. Malfunctioning nuclear weapons that are detonated with no nuclear yield (nuclear "duds") and installation of radionuclides in food or water are also possible means of generating a terror attack. The second and less probable scenario is the actual use of nuclear weapons. Each scenario has its own medical aspects, including "conventional" blast or thermal injury, introduction to a radiation field, and exposure to either external or internal contamination from a radioactive explosion.
Types of Radioisotopic Radiation
Isotopes of atoms with uneven numbers of protons and/or neutrons are typically unstable; such isotopes discharge particles or energy to matter, a process that is defined as radiation. The main radiation types are alpha, beta, gamma, and neutrons.
Alpha (α) radiation consists of heavy, positively charged particles that contain two protons and two neutrons. Alpha particles usually are emitted from isotopes with an atomic number of ≥82, such as uranium and plutonium. Due to their large size, alpha particles have limited penetrating power. Fine obstacles such as cloth and human skin usually can stop them from penetrating into the body, and they represent a small risk with external exposure due to their limited penetration. If they somehow are internalized, alpha particles can cause significant cellular damage in their immediate proximity.
Beta (β) radiation consists of electrons, which are small, light, negatively charged particles (about 1/2000 the mass of a neutron or proton). They can travel only a short finite distance in tissue, depending on their energy. Exposure to beta particles is common in many radiation accidents. Radioactive iodine released in nuclear plant accidents is the best known member of this group. Plastic layers and clothing can stop most beta particles, and their penetration is measured to be a few millimeters. A large quantum of energy to the basal stratum of the skin can cause a burn that is similar to a thermal burn and is treated as such.
Gamma (γ) rays and x-rays (both photons) are similar. Gamma rays are uncharged electromagnetic radiation discharged from a nucleus as a wave or photons of energy. X-rays are the product of abrupt mechanical deceleration of electrons striking a heavy target such as tungsten. Gamma rays and x-rays have similar properties, (i.e., no charge and no mass, just energy). Both travel easily through matter, sometimes called penetrating radiation, and are the principal type of radiation that causes total-body exposure. If the energy of gamma rays and x-rays is the same, their biologic effects will be the same.
Neutron (η) particles are heavy and uncharged, often emitted during nuclear detonation. They possess a wide energy range; their ability to penetrate tissues is variable, depending on their energy. They are less likely to be present in most scenarios of radiation bioterrorism.
The ionization resulting from protons, electrons, and gamma rays is either a direct or an indirect (i.e., mediated through water) effect of particles or photons on DNA. Ionization of DNA resulting from neutrons is secondary to the neutrons knocking electrons out of their atomic orbit and the formation of free radicals, which can also damage DNA directly.
The commonly used units of radiation are the rad and the gray (Gy). The rad (radiation absorbed dose) is energy deposited within living matter and is equal to 100 ergs/g of tissue.
The traditional rad has been replaced by the Syst`me Internationale (SI) unit of the gray; 100 rad = 1 Gy.
Whole-body exposure represents deposition of radiation energy over the entire body. Alpha and beta particles have limited penetration and do not cause significant noncutaneous injury unless emission results from an internalized source. Whole-body exposure from gamma rays, x-rays, or neutrons, which can penetrate through the body (depending on their energy), can result in damage to multiple tissues and organs. The tissue damage is proportional to the radiation exposure of the specific organ or tissue.
External contamination is a result of fallout of radioactive particles that land on the body surface, clothing, skin, and hair. This is the dominant element to consider in the mass casualty situation resulting from a radioactive terrorist strike. The common contaminants primarily emit alpha and beta radiation. Alpha particles do not penetrate beyond the skin and thus have minimal systemic effects. Beta emitters can cause significant cutaneous burns and scarring. Gamma emitters not only may cause local damage but also can cause whole-body radiation exposures and injury. The medical treatment is primarily decontamination of the body, including wounds and burns, to prevent the contamination from becoming internalized. Removing the contaminated clothing reduces the contamination significantly and is a first step in the decontamination process. Generally, patients will not constitute a significant radiation hazard to health care providers, and lifesaving treatment should not be delayed for fear of secondary contamination of the medical team. Any damage to health care personnel will depend directly on the duration of exposure and will be inversely proportional to the square of the distance from any radioactive source. Gowns that can be easily removed are essential to protect health care personnel.
Internal contamination will occur when radioactive material is inhaled or ingested or is able to enter the body through open wounds or burns or via skin absorption. In principle, any externally contaminated casualty should be evaluated for internal contamination. Some isotopes may have toxic effects on specific target organs due to their chemical properties, in addition to radiologic injury. The respiratory system is the main portal of entrance for internal contamination, and the lung is the organ at greatest risk. Aerosol particles <5 μm can reach the alveoli, whereas larger particles will remain in proximal airways. The tiny particles can be absorbed by the lymphatic system or the bloodstream. Bronchial lavage is often a helpful treatment in this situation. Radioactive material entering the gastrointestinal (GI) tract will be absorbed according to its chemical structure and solubility. The insoluble radionuclides may affect the lower GI tract. Intact skin is normally a good barrier to most radionuclides. Penetration through the skin usually takes place when wounds or burns have altered the skin barriers. Therefore, any skin erosion should be cleaned and decontaminated promptly.
Absorbed radioactive materials will travel throughout the body. Liver, kidney, adipose tissue, thyroid, and bone and bone marrow tend to bind and retain the radioactive material more than other tissues do. The medical treatment includes preventing absorption, reducing incorporation, and enhancing elimination (see below).
Localized exposure means close contact between a highly radioactive source and a part of the body, causing discrete damage to the skin and deeper tissues, similar to a thermal burn. Later signs include epilation, erythema, moist desquamation, ulceration, blistering, and necrosis in proportion to exposure. Alopecia, transient or permanent, is dose related and starts at cutaneous doses >3 Gy. Overt tissue damage can take weeks and even months to develop; the healing process can also be very slow, lasting for months. Long-term cutaneous changes, including keratosis, fibrosis, and telangiectasias, may appear years after the exposure. Treatment is based on analgesia and infection prophylaxis. Nevertheless, severe burns often require grafting or even amputation. Long-term radiation effects are characterized by cell loss and cell death.
Radiologic Dispersal Events
Radiologic dispersal incidents are generally of two types, resulting from (1) small, usually localized sources or (2) wide dispersals over large areas. The radioactive materials can take the form of solid state, aerosol, gas, or liquid. They can be put into food or water, released from vehicles, or be spread by explosion. The principal route of exposure is usually direct contact between the victim's skin and the radioactive particles, although internal contamination could occur if the material were inhaled or ingested. The radiation field is also a potential source of whole-body exposure. The psychosocial effects that accompany such an event are significant and are beyond the scope of this chapter. A list of radioactive materials, including information on their major properties and medical treatment, is given in Table 223-1.
Table 223-1 Internal Contaminant Radionuclides: Properties and Treatment |Favorite Table|Download (.pdf)
Table 223-1 Internal Contaminant Radionuclides: Properties and Treatment
|Isotope Name||Symbol||Common Usage||Radiation Type t½ Radiologic t½ Biologic, days||Exposure Type||Mode of Contamination||Focal Accumulation in Body||Treatment|
|Manganese||Mn-56||Reactors, research laboratories||β, γ 2.6 h 5.7||External, internal||N/A||Liver||N/A|
|Cobalt||Co-60||Medical radiotherapy devices, commercial food irradiators||β, γ 5.26 y 9.5||External, internal||Lungs||Liver||Gastric lavage, purgatives; penicillamine in severe cases|
|Strontium||Sr-90||Fission product of uranium||β 28 y 18,000||Internal||Moderate GI tract||Bones—similar to calcium||Strontium, calcium, ammonium chloride|
|Molybdenum||Mo-99||Hospitals—scans||β, γ 66.7 h 3||External, internal||N/A||Kidneys||N/A|
|Technetium||Tc-99m||Hospitals—scans||β, γ 6.049 h 1||External, internal||IV administration||Kidneys, total body||Potassium perchlorate to reduce thyroid dose|
|Cesium||Cs-137||Medical radiotherapy devices||β, γ 30 y 70||External, internal||Lungs, GI tract, wounds, follows potassium||Renal excretion||Ion-exchange resins, Prussian blue|
|Gadolinium||Gd-153||Hospitals||β, γ 242 d 1000||External, internal||N/A||N/A||N/A|
|Iridium||Ir-192||Commercial radiography||β, γ 74 d 50||External, internal||N/A||Spleen||N/A|
|Radium||Ra-226||Instrument illumination, industrial applications, old medical equipment, former Soviet Union military equipment||α, β, γ 1602 y 16,400||External, internal||GI tract||Bones||MgSO4 lavage, ammonium chloride, calcium alginates|
|Tritium||H-3||Luminescent gun sights, muzzle-velocity detectors, nuclear weapons||β 12.5 y 12||Internal||Inhalation, GI tract, wounds||Total body||Dilution with controlled water intake, diuretics|
|Iodine-131||131I||Reactor accidents, thyroid ablators||β, γ 8.1 d 138||Internal||Inhalation, GI tract, wounds||Thyroid||Potassium/sodium iodide, propylthiouracil, methimazole|
|Uranium||U-235||Depleted uranium, natural uranium, fuel rods, weapons-grade material||α, (α, β, γ) 7.1 × 108 y 15||Internal||GI tract||Kidneys, bones||NaHCO3, chelation with EDTA|
|Plutonium||Pu-239||Produced from uranium in reactors, nuclear weapons||α 2.2 × 104y 73,000||Internal||Limited lung absorption, high retention||Lungs, bones, bone marrow, liver, gonads||Chelating with DTPA or EDTA|
|Americium||Am-241||Smoke detectors, nuclear weapon detonation fallout||α 458 y 73,000||Internal||Inhalation, skin wounds||Lungs, liver, bones, bone marrow||Chelating with DTPA or EDTA|
|Polonium||Po-210||Calibration source||α 138.4 d 60||Internal||Inhalation, wounds||Spleen, kidneys||Lavage, dimercaprol|
|Thorium||Th-232||Calibration source||α 1.41 × 1010y 73,000||Internal||N/A||N/A||N/A|
|Phosphorus||P-32||Research laboratories, medical facilities||β 14.3 d 1155||Internal||Inhalation, GI tract, wounds||Bones, bone marrow, rapidly replicating cells||Lavage, aluminum hydroxide, phosphate|
In a localized event, the amount and spread of the radioactive materials are usually limited and can be treated like a spill of hazardous material. Protective clothing prevents or minimizes the contamination of emergency responders.
The use of explosives coupled with a large amount of radioactive materials can result in wide dispersion of radiation, which is of far greater concern. Other potential sources of radiation are nuclear reactors, spent nuclear fuel, and transport vehicles. Less probable but still possible is the use of a large source of penetrating radiation without explosion. It is expected that most exposures would be low, and the principal health and psychosocial effects would be similar to those in the former scenario but on a larger scale.
Whenever an explosion is involved, conventional lifesaving treatment should be given first priority. Only then should decontamination and specific treatment be given for the radiation exposure.
Silent exposure represents a scenario in which a powerful radiologic source, often also called a radiologic exposure device, could be hidden in a crowded place and spread radioactive materials without any awareness or announcement. It might take a long time to recognize the event and the source of exposure. One of the major clues to this situation is the appearance of unusual clinical manifestations in many individuals; such manifestations are often nonspecific and include symptoms of acute radiation sickness (see below) such as headache, fatigue, malaise, and opportunistic infections. GI phenomena such as diarrhea, nausea, vomiting, and anorexia may occur. Dermatologic symptoms (burns, ulceration, and epilation) and hematopoietic manifestations such as bleeding tendency, thrombocytopenia, purpura, lymphopenia, and neutropenia are also possible and are dose related. Careful epidemiologic studies may be necessary to identify the source of such exposure.
The most likely scenario of nuclear terror would be the detonation of a single low-yield device. The estimated yield of such a device is anywhere between 0.01 and 10 kilotons of TNT, although the probability more likely would be toward the lower yield. Coping with such an event is certainly possible. The effects of such an explosion are a combination of several components: ground shock, air blast, thermal radiation, initial nuclear radiation, crater formation, and radioactive fallout.
The nuclear detonation, like a conventional explosion, will produce a shock wave that can further damage structures and cause many casualties. In addition, the detonation can produce an extremely hot fireball that can ignite materials and cause severe burns. The detonation also releases an intense pulse of ionizing radiation, mainly gamma rays and neutrons. The radiation produced in the first minute is termed initial radiation, whereas the ongoing radiation due to fallout is termed residual radiation. Both types of radiation can cause acute radiation sickness. The LD50/30 (i.e., a dose that causes a 50% mortality rate at 30 days) is ∼4 Gy for whole-body exposure without medical support; with medical support, the LD50/30 ranges between 8 and 10 Gy. Winds can carry fallout and contaminate large areas.
On top of its effects, a massive blast forms a crater in the soil and usually produces a ground shock that compounds the damage and the number of casualties. Inhalation of large amounts of radioactive dust causes pneumonitis that can lead to pulmonary fibrosis. Use of a mask covering the mouth and nose can be very helpful. The intense flash of infrared and visible light can cause either temporary or permanent blindness. Cataracts can develop months to years later among those who survive.
Radiation interactions with atoms can result in ionization and the formation of free radicals that damage tissue by disrupting chemical bonds and molecular structures in the cell, including DNA. Radiation damage can lead to cell death; the cells that recover may be mutated and at higher risk for subsequent cancer. Cell sensitivity increases as the replication rate increases and cell differentiation decreases. Bone marrow and mucosal surfaces of the GI tract, which have vast mitotic activity, are significantly more sensitive to radiation than are slowly dividing tissues such as bones and muscles. After exposure of either all or most of the human body to ionizing radiation, acute radiation syndrome (ARS) can develop. The clinical manifestations of ARS reflect the dose and type of radiation as well as the part of the body exposed.
ARS manifests as three major groups of signs and symptoms: hematopoietic, GI, and neurovascular. There are four major stages in ARS: prodrome, latent phase, illness, and recovery or death. The higher the radiation doses, the shorter and more severe each stage. The prodrome appears within minutes to 4 days after exposure, lasts from a few hours to a few days, and can include nausea, vomiting, anorexia, and diarrhea. At the end of the prodrome, ARS progresses to the latent phase. Minimal or no symptoms are present during the latent phase, which commonly lasts up to 2.5 weeks but can last up to 6 weeks. The duration depends on the radiation dose, the health of the patient, and the coexisting illness or injury. After the latent phase, the exposed person manifests illness that may eventuate in recovery or lead to death.
With exposure to doses <1 Gy, ARS is generally mild. At this dose symptoms can be minimal or nonexistent even if the entire body is exposed to penetrating radiation. The clinical picture will mainly be transient depression of bone marrow (lymphopenia) that lasts up to 2 to 3 weeks and then improves.
ARS is significantly more acute and severe with exposure to very high doses: >30 Gy. At this dose the prodrome appears in minutes and is followed by 5 to 6 hours of latency before a cardiovascular collapse occurs secondary to irreversible damage to the microcirculation.
The type and dose of radiation and the part of the body exposed will determine not only the timing of the different stages of ARS but also the dominant clinical picture. At low radiation doses of 0.7–4 Gy, hematopoietic depression due to bone marrow suppression takes place and constitutes the main illness. The patient may develop infections and bleeding secondary to low leukocyte and platelet counts, respectively. The bone marrow eventually will recover in almost all patients if they are supported with transfusions and fluids; antibiotics are often needed in addition. With exposure to 6–8 Gy, the clinical picture is significantly more complicated. At these doses, the bone marrow will not always recover and death may ensue. A GI syndrome may accompany the hematopoietic manifestations and further worsen the patient's condition. Compromise of the absorptive layer of the gut alters absorption of fluids, electrolytes, and nutrients. GI injury can lead to vomiting, diarrhea, GI bleeding, sepsis, and electrolyte and fluid imbalance in a patient whose blood counts are compromised for a period of weeks, often leading to death. Whole-body exposure to doses >9–10 Gy is almost always fatal. Crucial elements of the bone marrow simply will not recover. In addition to the GI syndrome associated with very large exposures, patients may develop a neurovascular syndrome; the latter dominates with whole-body doses >20 Gy. Vascular collapse, seizures, confusion, and death usually occur within days. In this variant the prodrome and latent phase both shorten to a few hours.
Treatment: Acute Radiation Sickness
The treatment of ARS is focused on maintaining homeostasis, giving damaged organs a chance to recover. Aggressive support is given to every damaged system. Treatment for the hematopoietic system includes mainly therapy for neutropenia and infection, transfusion and blood products such as leukoreduced irradiated blood as needed, and hematopoietic growth factors. The value of bone marrow transplantation in this situation is questionable. None of the transplants that were performed among the victims of the nuclear reactor accident in Chernobyl proved successful. Bone marrow transplantation could be considered for casualties with whole-body exposure to 6–10 Gy when the hematopoietic syndrome is dominant and the bone marrow is less likely to recover with time. Another major component of the treatment of ARS is partial or total parenteral nutrition to bypass the damaged GI system. For blast and thermal injuries, standard therapy for trauma is given. Psychological support is essential in many cases.
Medical Management of Radiation Bioterrorism
Victims of radiation bioterrorism can suffer from conventional thermal or blast injuries, exposure to radiation, and contamination by radioactive materials. Many will have combinations of the above, which can be synergistic and cause higher morbidity and mortality rates than is the case when they occur alone. The number of casualties will be a major factor in determining the response of the medical system to an act of radiation bioterrorism. If only a few persons are affected, no significant changes and adaptation of the system are needed to treat the victims. However, if a terror attack results in a large number (dozens or more) of casualties, an organized disaster plan at the local and state levels must be invoked to deal with the crisis properly. Useful U.S. planning documents that include many universal planning concepts can be found at http://www.remm.nlm.gov/remm_Preplanning.htm. Medical personnel should have a prior assignment and training and be prepared to function in a scenario with which they are familiar. Stockpiles of specific equipment and medications have to be preplanned (see the Centers for Disease Control and Prevention Web site at http://www.bt.cdc.gov/stockpile/). One of the goals of terrorists is to overwhelm medical facilities and minimize the salvage of casualties.
Initial management consists of primary triage and transportation of the wounded to medical facilities for treatment. The rationale behind the triage is to sort patients into classes according to the severity of injury for the purpose of expediting clinical care and maximizing the use of the available clinical services and facilities. Triage requires determination of the level of emergency care needed. The higher the number and range of casualties are, the more complex and difficult triage becomes. The mildly wounded and victims of contamination only can be sent to evacuation, registration with disaster response teams, and decontamination and treatment centers. Figure 223-1 illustrates evacuation in a multicasualties radiologic event. In this way, the hospitals can avoid being directly overwhelmed, and those who are severely wounded can receive better treatment. Emergency treatment will be administered initially according to the presence of conventional injuries such as wounds, trauma, and thermal or chemical burns. Individuals with such injuries should be stabilized, if possible, and immediately transported to a medical facility. Removing the victim's clothes and wrapping him or her in clean blankets or nylon sheets reduces both the exposure of the patient and the contamination risk to the staff. However, the possibility of contamination needs to be determined. Less severely injured victims should receive a preliminary decontamination before or during evacuation to a hospital.
Algorithm for evacuation in a multicasualties radiologic event.
One must remember that radionuclide contamination of the skin is commonly not an acute life-threatening situation for the patient or the personnel who care for the patient. Only powerful gamma emitters are likely to cause real damage from contamination. It is important to emphasize that exposure to a radiation field alone does not necessarily create any contamination. The exposed person, if not contaminated, is not radioactive and does not directly emit any radiation.
To protect the staff, protective gear (gowns, gloves, masks, and caps) should be used. Protective masks with filters and chemically protective overgarments provide excellent protection from contamination. Waterproof shoe covers are also important. Remaining in the contaminated area and dealing with lifesaving procedures should take place according to the "ALARA" principle: as low as reasonably achievable. It is better to send many people for short exposure times than to send a few people for longer periods of time to do the same job.
Decontamination of victims should take place in the field before their arrival at medical facilities, but radiologic decontamination should never interfere with medical care. Removal of outer clothing and shoes usually will reduce a patient's contamination by 80–90%. Contaminated clothes should be carefully removed by rolling them over themselves, placing them in marked plastic bags, and removing them to a predefined area for contaminated clothes and equipment. A radiation detector should then be used to check for the presence of any residual radiologic contamination on the patient's body. To prevent internalization of the radioactive materials, one should cover open wounds before decontamination. Showering or washing of the entire skin and hair is very important. The skin is dried and reassessed for residual contamination until no radiation is found. Contamination-removing chemical agents are more than sufficient to remove radiologic contamination.
Wound decontamination should be as conservative as possible. The main goal is to prevent both extensive local damage and internal contamination through lacerated skin. The bandages should be removed, and the wounds flushed. The wound should then be dried and assessed for radiation. This procedure can be repeated again and again until contamination is undetectable. Excision of contaminated wounds should be attempted only when surgically necessary. Radioactive shrapnel that can penetrate through the skin should be removed.
In the hospital, staff can wear normal hospital barrier clothing, including two pairs of gloves, a gown, shoe covers, a head cover, and a face mask. Eye protection is recommended. Decontamination of medical personnel is obligatory after emergency treatment and decontamination of the patient. All protective clothing should be placed after use in a designated container for contaminated clothing.
Radiation intensity decays rapidly with the square of the distance from the source, and increasing the distance from the source and decreasing the time spent near it are basic principles of radiation safety. Shielding with lead can be used as protection from small radioactive gamma sources. Geiger counters can detect gamma and beta radiation. Pocket chamber (pencil) dosimeters, film badges, and thermoluminescent dosimeters can measure accumulated exposure to gamma radiation. All these detectors are in common use in medical facilities and should be used to help define the level of contamination. Alpha radiation is harder to detect due to its poor penetration. An alpha scintillation counter, which is capable of detecting alpha radiation, is not commonly used in medical facilities.
Guidelines for Hospital Management
Figure 223-2 shows a model for hospital arrangement for triage. Persons contaminated either externally or internally should be identified, externally decontaminated, and, if needed, treated immediately and specifically for internal contamination. In all other cases, the need for treatment of radiation injuries does not constitute a medical emergency. Early actions, such as blood sampling both for assessing the degree of severity of the exposure and for blood type and cross-matching for possible transfusion, need to be taken promptly if ARS is evident or if exposure is suspected.
Flow chart of hospital triage. O.R., operating room.
In the hospital entrance, a distinct decontamination area should be set up promptly. Separation between clean and contaminated areas is essential. Medical personnel in this area should wear protective gear as noted above. They also should be rotated in their assignments every 1 to 2 hours to ensure minimal exposure to radiation. If patients are critically wounded and require either surgery or resuscitation, they need to pass directly to "contaminated" operating rooms or resuscitation sites for lifesaving procedures. Once such patients are stable, they should be decontaminated. It is important to obtain details concerning the exposure, look for prodromal signs of radiation sickness, and do a physical examination. One of the best ways to estimate exposure clinically is to measure the time of prodromal appearance. The earlier the prodromal signs and symptoms appear, the higher the dose is of radiation exposure. A few laboratory tests need to be taken routinely, such as complete blood count and urinalysis. If internal contamination is suspected, specific treatment should be given, as outlined below.
Treatment: Radionuclide Contamination
Treatment for internal radionuclide contamination, decorporation, should be started as soon as possible after suspected or known exposure. The approximate upper limit of radionuclide contamination that can reasonably be ignored from a radiation safety point of view is not well defined. These are judgments that will depend on the circumstances of the event and the resources available. One method to determine a level of internal contamination that will trigger decorporation would be the upper limit of the yearly radionuclide contamination permitted for radiation workers [allowable levels of intake (ALIs)]. Radiation workers are permitted 50 times more radiation dose each year than are members of the general public. A new concept called the Clinical Decision Guide is contained in the National Council on Radiation Protection and Measurements (NCRP) Report 161 and is expected to replace the use of ALI.
The goal is to leave the smallest amount of radionuclides possible in the body. Treatment is given to reduce absorption and enhance elimination and excretion. Some of the decorporation agents are not U.S. Food and Drug Administration (FDA)-approved for these indications, and there is very little clinical data to support the efficacy of their use.
Clearance of the GI tract may be achieved by stomach lavage, with emetics (such as apomorphine, 5 to 10 mg, or ipecac, 1- to 2-g capsules or 15 mL in syrup), or by using purgatives, laxatives, ion exchangers, and aluminum antacids. Prussian blue, 1 g tid for a minimum of 3 weeks, is an ion exchanger used to treat cesium 137 internal contamination. Aluminum antacids (such as aluminum phosphate gel) may reduce strontium uptake in the gut if given immediately after exposure. Aluminum hydroxide is less effective.
Prevention or reversal of radionuclide interaction with tissues can be done by blocking, diluting, mobilizing, and chelating agents. Blocking agents prevent the entrance of radioactive materials. A good example is potassium iodide (KI), which blocks the uptake of radioactive iodine (131I) by the thyroid. KI is most effective if taken within the first hour after exposure and is still effective 6 hours after exposure. The effectiveness subsequently declines until 24 hours after exposure; however, it is recommended that KI be taken up to 48 hours after exposure. The KI dose is based on age, predicted thyroid exposure, and pregnancy and lactation status. Adults between the ages of 18–40 should receive 130 mg/d for 7–14 days if exposed to ≥10 cGy of radioactive iodine. Other thyroid-blocking agents include prophylthiouracil, 100 mg tid for 8 days, and methimazole, 10 mg tid for 2 days followed by 5 mg tid for 6 days, but they are somewhat less effective.
Diluting agents decrease the absorption of the radionuclide; for example, water may be used as a diluting agent in the treatment for tritium (3H) contamination. The recommended amount is 3–4 L/d for at least 3 weeks.
Mobilizing agents are most effective when given immediately; however, they may be effective for up to 2 weeks after exposure. These agents include antithyroid drugs, parathyroid extract, glucocorticoids, ammonium chloride, diuretics, expectorants, and inhalants. All of them should induce the release of radionuclides from tissues.
Chelating agents can bind many radioactive materials, after which the complexes are excreted from the human body. In this regard, diethylenetriaminepentaacetic acid (DTPA) as either Ca-DTPA or Zn-DTPA is superior to ethylenediamine tetraacetic acid (EDTA); DTPA was approved by the FDA to treat internal contamination with plutonium, americium, and curium, but it also chelates berkelium, californium, and any material with an atomic number >92. Ca-DTPA is more effective than Zn-DTPA during the first 24 hours after internal contamination, and both drugs are equally effective after the initial 24 hours. If both drugs are available, Ca-DTPA should be given as the first dose. If additional treatment is needed, treatment should be switched to Zn-DTPA. The dose is 1 g Ca-DTPA or Zn-DTPA, dissolved in 250 mL of normal saline or 5% glucose, given intravenously over 1 hour daily. The duration of chelation treatment depends on the amount of internal contamination and the individual response to treatment. DTPA also can be administrated by nebulized inhalation; 1 g is given in 1:1 dilution with water or saline over 15–20 minutes. Nebulized Zn-DTPA is recommended if the internal contamination is only by inhalation. The IV route is recommended and should be used if the route of internal contamination is not known or if multiple routes of internal contamination are likely. Treating uranium contamination with DTPA is contraindicated due to its synergistic damage to the kidneys.
Lung lavage can reduce radiation-induced pneumonitis and is indicated only when a large amount of radionuclide enters the lungs and has the potential for acute radiation injury. The procedure requires anesthesia. Table 223-2 summarizes the common treatment regimens for internal radionuclide contamination.
Table 223-2 Common Drugsa for Treatment of Internal Contamination |Favorite Table|Download (.pdf)
Table 223-2 Common Drugsa for Treatment of Internal Contamination
|Medication||Administered for Radionuclides||Route of Administration||Dosage||Duration||Mechanism of Action|
|KI||131I||PO||130 mg/d for adults >40 with thyroid exposure >500 cGy; 130 mg/d for adults 18–40 with thyroid exposure >10 cGy; 130 mg/d for pregnant or lactating women with thyroid exposure >5 cGy; 65 mg/d for children and adolescents 3–18 with thyroid exposure >5 cGy; 32.5 mg/d for infants 1 mo to 3 y with thyroid exposure >5 cGy; 16 mg/d for neonates from birth to 1 mo with thyroid exposure >5 cGy||7–14 d||Blocking agent|
|Zn-DTPA||Plutonium, trans-plutonium, yttrium, americium, curium||IV||1 g in 250 mL NS or 5% glucose, given in 1–2 h, or bolus over 3–4 min||Up to 5 d||Chelating agent|
|Inhalation||1 g in 1:1 dilution with water or NS over 15–20 min|
|IM||1 g; not recommended because of pain|
|Ca-DTPA||Plutonium, trans-plutonium, yttrium, americium, curium||IV||1 g in 250 mL NS or 5% glucose, given in 1–2 h, or bolus over 3–4 min||Up to 5 d||Chelating agent|
|Inhalation||1 g in 1:1 dilution with water or NS over 15–20 min|
|IM||1 g; not recommended because of pain|
|Bicarbonate||Uranium||IV||2 ampoules sodium bicarbonate (44.3 meq each, 7.5%) in 1000 mL NS, 125 mL/L, or 1 ampoule of sodium bicarbonate (44.3 meq, 7.5%) in 500 mL NS, 500 mL/h||Usually IV for the first 24 h, PO for additional 2 d; continuation of treatment for >3 d is rare and can be done according to titration of uranium amounts in the body||Increased excretion via the kidneys|
|PO||2 tablets every 4 h until urine pH = 7–8, or 4 g (8 tablets) 3 tid|
|Prussian blue||Cesium-137||PO||1 g tid with 100–200 mL water, up to 10 g/d||=3 wk titrated by urine and fecal bioassay and whole-body counting||Ion exchanger|
|Water||Tritium (H-3)||PO||>3–4 L per d||3 wk||Excretion of water|
|Aluminum phosphate gel||Strontium||PO||100 mL immediately after exposure||Once||Decreased gut absorption|
|Aluminum hydroxide||PO||60–100 mL||Once||Decreased gut absorption|
Medical Assay of the Radiation-Exposed Patient
One of the major difficulties in treating victims exposed to radiation is determination of the amount of exposure. Clinical assessment of the patient is the best approach. Biodosimetry, when available, can lead to better assessment of the level of exposure. The clinical assessment is based primarily on the timing and severity of the prodrome of ARS. Appearance of an early prodrome indicates high exposure to radiation. Victims who arrive at the hospital complaining of severe weakness, nausea, vomiting, diarrhea, or seizures probably will not survive despite supportive measures. Decontamination and the use of radiation-detection equipment are both very important. Few tests can be performed to estimate the radiation exposure and the contamination. Biodosimetry Assessment Tool (BAT) is a tool to aid treatment decisions during radiation exposure incidents; it was developed by the U.S. Armed Forces Radiobiology Research Institute (http://www.afrri.usuhs.mil). Baseline laboratory tests should include a complete blood count with differential and platelet count, renal evaluation, and determination of electrolytes. Urine and stool samples should be obtained if internal contamination is suspected. Nasal swabs should be taken from each nostril for determination of inhalation of radionuclides. The nasal swabs are useful if taken within the first 1–2 hours after the exposure. After exhalation, each swab is labeled and sealed in a plastic bag and sent for analysis to appropriate laboratories. Patients exposed to 0.7–4 Gy will develop pancytopenia from as early as 10 days to as long as 8 weeks after exposure. Lymphocytes show the most rapid decline, whereas other leukocytes and platelets decline less rapidly. Erythrocytes are the least vulnerable blood elements.
Absolute lymphocyte counts should be taken every 4–6 hours for 5–6 days; they are the most valuable early indicator because they are recognized to be a sensitive marker for radiation damage and correlate with both the exposure and the prognosis. A 50% drop in absolute lymphocyte count within the first 24 hours indicates a significant injury. HLA typing is necessary whenever there is suspicion of irreversible bone marrow damage. Lymphocyte chromosomal analysis can detect radiation exposure as low as 0.03–0.06 Gy, and 15 mL of blood should be drawn as early as possible in a heparinized collection tube and kept cool. Radiation-induced chromosomal aberrations in peripheral blood lymphocytes include dicentric chromosomes and ring forms that last for a few weeks. Calibration of a dose-response curve makes it possible to assess the radiation dose. Dicentric quantification requires multiple days to perform and is available only in select centers.
Another method for estimating exposure is the in vitro cytokinesis-block micronucleus assay. Micronuclei can be the result of small acentric chromosome fragments that arise during exposure to radiation. The technique to score the micronuclei in peripheral blood lymphocytes has been standardized in the last few years. It can be a useful tool in small-scale exposure but is not feasible in a mass casualty setting. An algorithm for the treatment of radiation casualties is shown in Fig. 223-3.
General guidelines for treatment of radiation casualties. CBC, complete blood count.
It is desirable to continue follow-up in some circumstances. In general, only persons who are exposed to <8–10 Gy whole-body irradiation have a chance to survive in the long term, and they are at risk of developing cataracts, sterility, and lung, kidney, and bone marrow problems. Based on their age, their gender, and the amount and type of exposure, they should be followed for many years. A major public health issue is the risk of secondary malignancy in individuals and populations that were exposed to low doses of radiation. Leukemia and breast, brain, thyroid, and lung cancer are the most common, but the exposed population is at increased risk for many other cancers as well. Appropriate follow-up protocols should be developed, based on the type of exposure and the exposed population. In cases of internal contamination, the long-term follow-up should be focused on the organ at risk. Such is the case with uranium contamination, with its nephrotoxic properties.