Acute Radiation Research Papers
Acute Radiation Syndrome Acute radiation syndrome which is also sometimes known as radiation sickness or radiation toxicity is an extremely serious illness that occurs when the entire body (or most of it) receives a high dose of penetrating radiation, a dose greater than 50 rads, in a very short period of time. Studies in animals and humans exposed to radiation have allowed researchers to describe acute radiation syndrome. The most replicative cells are the most sensitive to the acute effects of radiation, particularly spermatocytes, lymphohematopoeitic elements, and intestinal crypt cells. The inherent sensitivity of these cells results in a constellation of clinical syndromes that predominates within a predictable range of doses of whole-body
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or significant partial-body exposure. People exposed to radiation will get acute radiation syndrome only if the following conditions are satisfied: the radiation dose was high; the radiation was penetrating; the person’s entire body, or most of it, received the does; and the radiation was received in a short time, usually within minutes. Doses from medical procedures such as x-rays are too low to cause acute radiation syndrome; however, doses from radiation therapy to treat cancer may be high enough cause some symptoms. The radiation must come from an external source such as high energy gamma-rays and penetrate to internal organs. The person’s entire body, or most of it, most be exposed acutely, that is, in a matter of seconds or minutes. Examples of people who suffered from acute radiation syndrome are the survivors of the Hiroshima and Nagasaki atomic bombs (image to the left contains a Japanese girl recovering from the effects of radiation sickness), the firefighters the first responded after the Chernobyl Nuclear Power Plant 1986 event, and some unintentional exposures to sterilization irradiators.
The main consequence of an acute radiation exposure is a decrease in life span of the exposed organism. The decrease in life span has a positive correlation with the dose of radiation exposure. Because there are high variations in survival times between different species and between animals within the same species, organism survival times are expressed as the average survival time which takes the many variations into consideration. A value known as the lethal dose is used to describe the relationship of survival of a whole population of the same species exposed to the same dose compared to the percentage of the population that will be killed from that same dose within a given period of time. To illustrate, the lethal dose required to kill fifty percent of a population in thirty days is expressed as LD 50/30. Table 4-1 lists the LD 50/30 doses in rads for several species.
For humans, a LD 50/60 is more useful since humans usually survive over thirty days of the radiation exposure. The LD 50/60 for humans is approximately 250-300 rads. The dose of radiation exposure has an inverse relationship with the survival time. A mammalian dose survival curve can be seen below; one can deduce the fact that as the radiation dose goes up, the survival time and number of survivors decreases.
In referring to the three regions of the mammalian dose survival curve above, there are three different systems that can result in death to the animal. Other organs and systems have suffered damage, but the principal cause of death is destruction to one specific system. The three defined acute radiation syndromes are named according to failure of that organ system which causes death: the bone marrow (hematologic) syndrome, the gastrointestinal syndrome, and the cardiovascular/central nervous system syndrome.
Depending on the absorbed dose, symptoms appear within hours to weeks, following a predictable clinical course. The signs and symptoms that develop in acute radiation syndrome occur through four distinct phases: prodromal phase, latent phase, manifest illness stage, and recovery of death phase. The prodromal phase of the acute radiation syndrome usually occurs in the first 48 hours may develop up to six days after initial exposure. The prodromal stage is also known as the N-V-D stage named after the classic symptoms of the stage: nausea, vomiting, as well as anorexia and possibly diarrhea depending on dose. After high radiation doses, additional symptoms such as prostration, fever, respiratory difficulties, and increased excitability may develop. This is the stage at which most victims seek medical care. The second stage, the latent stage, is the transitional period in which many of the initial symptoms resolve, and may last for up to 3 weeks depending on the original radiation dose. This time interval decreases as the initial dose increases. After the latent stage, the manifest illness stage is the period of time when overt illness develops, often characterized by infection, bleeding, electrolyte imbalance, diarrhea, changes in mental status, and shock. During this stage, the exposed organism will show signs and symptoms of the specific syndrome reflecting the organ system that is damaged. The manifest illness stage lasts from minutes to weeks depending on the dose. The last stage, the recovery or death phase, follows the period of overt illness, which may take weeks or months to resolve. The effected animal will either recover or die in this stage as a result of the damage sustained from the initial radiation exposure. These stages are described in further detail in the table below.
Acute Radiation Syndromes | Syndrome | Dose* | Prodromal Stage | Latent Stage | Manifest Illness Stage | Recovery | Hematopoietic
(Bone Marrow) | > 0.7 Gy (> 70 rads)
(mild symptoms may occur as low as 0.3 Gy or 30 rads) | • Symptoms are anorexia, nausea and vomiting.
• Onset occurs 1 hour to 2 days after exposure.
• Stage lasts for minutes to days. | • Stem cells in bone marrow are dying, although patient may appear and feel well.
• Stage lasts 1 to 6 weeks. | • Symptoms are anorexia, fever, and malaise.
• Drop in all blood cell counts occurs for several weeks.
• Primary cause of death is infection and hemorrhage.
• Survival decreases with increasing dose.
• Most deaths occur within a few months after exposure. | • in most cases, bone marrow cells will begin to repopulate the marrow.
• There should be full recovery for a large percentage of individuals from a few weeks up to two years after exposure.
• death may occur in some individuals at 1.2 Gy (120 rads).
• the LD50/60† is about 2.5 to 5 Gy (250 to 500 rads) | Gastrointestinal (GI) | > 10 Gy (> 1000 rads)
(some symptoms may occur as low as 6 Gy or 600 rads) | • Symptoms are anorexia, severe nausea, vomiting, cramps, and diarrhea.
• Onset occurs within a few hours after exposure.
• Stage lasts about 2 days. | • Stem cells in bone marrow and cells lining GI tract are dying, although patient may appear and feel well.
• Stage lasts less than 1 week. | • Symptoms are malaise, anorexia, severe diarrhea, fever, dehydration, and electrolyte imbalance.
• Death is due to infection, dehydration, and electrolyte imbalance.
• Death occurs within 2 weeks of exposure. | • the LD100‡ is about 10 Gy (1000 rads) | Cardiovascular (CV)/ Central Nervous System (CNS) | > 50 Gy (5000 rads)
(some symptoms may occur as low as 20 Gy or 2000 rads) | • Symptoms are extreme nervousness and confusion; severe nausea, vomiting, and watery diarrhea; loss of consciousness; and burning sensations of the skin.
• Onset occurs within minutes of exposure.
• Stage lasts for minutes to hours. | • Patient may return to partial functionality.
• Stage may last for hours but often is less. | • Symptoms are return of watery diarrhea, convulsions, and coma.
• Onset occurs 5 to 6 hours after exposure.
• Death occurs within 3 days of exposure. | • No recovery is expected. | * The absorbed doses quoted here are “gamma equivalent” values. Neutrons or protons generally produce the same effects as gamma, beta, or X-rays but at lower doses. If the patient has been exposed to neutrons or protons, consult radiation experts on how to interpret the dose.
† The LD50/60 is the dose necessary to kill 50% of the exposed population in 60 days.
‡ The LD100 is the dose necessary to kill 100% of the exposed population | |
The bone marrow syndrome, also referred to as the hematologic or hematopoietic syndrome, occurs between 100-1,000 R range, with death occurring within six to eight weeks in some individuals at a dose of 200 R. This syndrome is exhibited by destruction of bone marrow caused by a reduction of red and white blood cells and platelets resulting from radiation exposure. The bone marrow syndrome is characterized by anorexia (lack of appetite), fever, malaise, sepsis, and hemorrhagic complications. The hematopoietic system shows the earliest indication of the severity of the radiation exposure through the rapidity and degree of drop in the cell count which includes lymphocytes, granulocytes, thrombocytes, and reticulocytes. The reduction in cell count causes the symptoms associated with this syndrome. The absolute lymphocyte count at 48 hours after initial exposure is a good predictor for prognosis. To illustrate, if the total lymphocyte count is greater than 1,200 it is unlikely that the effected patient has received a lethal dose. If at 48 hours the lymphocyte cell count is between 300 and 1,200, a significant exposure has occurred and the patient should be hospitalized with barrier protection isolation. Lymphocyte levels of lass then 300 cell per/ml are usually critical and warrant the consideration of the use of colony-stimulating factors on an individual basis. For people suffering with this syndrome, survival time is dose dependent. In the range of 100-300 R, the bone marrow repopulates enough to sustain life in most individuals.
The gastrointestinal syndrome appears in all animals at doses between 1,000 and 10,000 range.
Symptoms in this system are regularly seen at a threshold dose of 600 rads and result from damage to the epithelial cells lining the intestinal tract. The higher the exposure, the sooner the symptoms of nausea and vomiting develop. The presence of these symptoms typically overlaps with the drop in the cell count described previously. As a result, sepsis, loss of fluids, electrolytes and opportunistic infections complicate the picture. Persistent high fevers and bloody diarrhea is an ominous sign despite fluid and electrolyte replacement. Survival time in this syndrome does not vary with dose. Death happens at the same time regardless of dose. Human death occurs within three to ten days without medical support and within approximately two weeks with medical …show more content…
intervention.
Central nervous system symptoms are seen with acute radiation doses in excess of 1000 rads and are probably due to diffuse microvascular leaks within the brain. Damage to these blood vessels result in the loss of fluids and electrolytes, edema, increased intracranial pressure, and death. This injury is irreversible and the victim rarely lives long enough to suffer any hematological or gastrointestinal symptoms. Symptoms of shock may develop quickly in these patients. The central nervous system syndrome occurs at doses greater than 5,000 rads in humans. Death is usually within hours, but may occur two to three days post-exposure. Depending on the dose, the prodromal stage lasts from a few minutes to a few hours. The person suffers nervousness, confusion, nausea and vomiting, a loss of consciousness, and burning sensations of the skin. A latent period may last several hours. Manifest illness occurs five to six hours after exposure, resulting in diarrhea, convulsions, coma, and death.
All organs and body tissues can be affected by partial body irradiation. The result is death to some of the cells, which results in atrophy or shrinking of the tissue or organ. Although recovery is possible, atrophy may lead to the effected organ or tissue becoming nonfunctional. With high enough doses, any local tissue will react. Tissue response depends on its radiosensitivity, reproduction, and maturation rates. Due to the early uses of radiation and radiation therapy, the effects of radiation on the skin are very well understood. Various skin changes occur depending on the radiation dose. The injuries tend to progress with dose level and there appears to be a threshold effect for these clinical signs. Early erythema, reddening of the skin, is an early indicator that someone has had too much radiation exposure. At doses around 300 rads, erythema will develop within a few hours, but more importantly, it can appear within a few hours only to reappear at a later time. Therefore, the effected person should be examined on an hourly basis for this sign and ideally photographs should be taken to document this sign. If local radiation dermatitis develops with this sign, the dose is in the region of 1,000 rads. If blistering occurs then the dose is in the range of 1,500 rads. Also, if necrosis develops, the dose is in the region of greater than 5,000 rads. Therefore, by noting these clinical signs, one is able to establish the approximate dose range the patient was subjected to and these doses would be confirmed by dosimetry at a later stage. The table below further describes radiation effects on the integumentary system.
The diagnosis of acute radiation syndrome in a patient without a confirmed history of acute exposure to ionizing radiation can be very difficult due to the nonspecific nature of symptoms. A complete blood count (CBC) should be collected at time of patient presentation and repeated regularly (every four hours for the first eight hours, then every six hours for the following 40-48 hours), and absolutely lymphocyte count should be measured. The table below illustrates lymphocyte depletion curves and accompanying clinical severity ranges.
An initially low or rapidly falling lymphocyte count is indicative of a high dose of radiation. Estimation of exposure is important as this information is needed to guide treatment decisions. Information about estimated radiation dose and hence severity of radiation illness can also be inferred on the basis of time to onset of vomiting, which is typically inversely related to absorbed dose, although at lower doses this information is less reliable. Onset of vomiting ranges from less than ten minutes at an estimated dose of 8 Gy ir higher, to greater than two hours at doses of less than 2 Gy. As emesis may be symptomatic of a range of other conditions, patients should also be assessed for the presence of other adverse health effects that would support a diagnosis of acute radiation syndrome. See the table below for an estimation of dose related to onset of vomiting for single acute exposure of radiation.
Cytogenetic dosimetry is the gold standard and only accurate method of determining radiation dosing. The test is based on predictable and standardized effects of radiation on the replication of deoxyribonucleic acid (DNA) in lymphocytes. However, cytogenetic dosimetry is not widely available and results take several days to process.
Patients with acute, high dose, whole body irradiation will fall into one of three categories: those who recover with minimal intervention; those who require aggressive supportive care, up to and including bone marrow stem cell transplants; and those who – due to the dose they received, concomitant physical trauma, or inadequate clinical resources – will be triaged to receive palliative care. Except for the moribund individual, patient management during the prodromal phase is fairly uniform, regardless of triage category. Obtaining a history and physical examination, removal of external contamination, dose estimation, supportive care (including psychological support of the patient and family), symptomatic treatment, and replacement of fluids and electrolytes should be the earliest goals of medical management. With the onset of the latent phase, medical staff should have at least a crude estimate of absorbed dose and illness severity. Individuals with hematopoietic syndrome should be transferred to tertiary care centers specializing in the care of pancytopenic patients. Physical trauma or burn injury superimposed on radiation exposure predisposes victims to a worse overall prognosis. Individuals with such combined injuries, along with those whose clinical picture suggests an even higher absorbed dose, should be provided with comfort care in order to alleviate pain and suffering.
Over the first week to 10 days postexposure – as granulocytes begin to decrease towards a nadir – it is critical to support neutrophil levels. As the number of neutrophils falls, the likelihood of infection increases. Patients most at risk are those with neutrophil counts <0.5 × 109cells/liter. Consultations with infectious disease specialists and hematologists are recommended if febrile neutropenia develops.2,12Strict infection control can and should be supplemented as soon as possible by administration of cytokines: granulocyte colony stimulating factor (G-CSF) or granulocyte-macrophage colony stimulating factor (GM-CSF). These drugs stimulate neutrophil precursor cells in the bone marrow to divide and produce mature cells. Subpopulations of radioresistant bone marrow stem cells unaffected by ionizing radiation and pools of hematopoietic stem cells spared by shielding provide an intrinsic reservoir for recovery, especially when enhanced by the use of cytokines and intensive supportive care.13
Neither G-CSF nor GM-CSF has been approved for use by the US Food and Drug Administration (FDA) as a treatment for radiation-induced neutropenia. Nevertheless, the “non-approved” use of G-CSF (filgrastim or Neupogen®), GM-CSF (Leukine®, Leucotropin®), or the pegylated form of G-CSF (peg-filgrastim or Neulasta®) has been recommended by the Strategic National Stockpile (SNS) Radiation Working Group and by other experts in radiation medicine.5 The Centers for Disease Control and Prevention (CDC), which has oversight for the SNS, currently holds an Investigational New Drug application with the FDA for the release and use of Neupogen® following a radiation mass casualty event. Bone marrow stem cell transplants can be considered for whole body absorbed doses of 700 to 1000 rad (7 to 10 Gy). The Radiation Injury Treatment Network (http://bloodcell.transplant.hrsa.gov/ABOUT/RITN/index.html) was developed to respond to potential disasters where victims may suffer overwhelming bone marrow damage.
The CDC has produced a broad range of educational products including fact sheets, satellite broadcasts, videos, and CD-ROMs (http://www.bt.cdc.gov/radiation/).
The Radiation Event Medical Management (REMM) web portal (http://remm.nlm.gov/), developed under the auspices of the US Department of Health and Human Services, includes guidance for health care providers. Finally, radiation emergency medicine consultation services are provided by the Radiation Emergency Assistance Center/Training Site (REAC/TS). REAC/TS physicians and health physicists are available 24 hours a day, 7 days a week at 865.576.1005 (http://orise.orau.gov/reacts/).
Health care providers may yet be called upon to provide care to victims of acute, high-dose, ionizing radiation exposure following a terrorist radiation event. ARS, a consequence of such an exposure, will be assessed and managed on the basis of a thorough history and physical examination, diagnostic testing, and appropriate resource allocation. Even with proper management, recovery from ARS takes a long time and lifelong medical follow up is
essential.
or significant partial-body exposure. People exposed to radiation will get acute radiation syndrome only if the following conditions are satisfied: the radiation dose was high; the radiation was penetrating; the person’s entire body, or most of it, received the does; and the radiation was received in a short time, usually within minutes. Doses from medical procedures such as x-rays are too low to cause acute radiation syndrome; however, doses from radiation therapy to treat cancer may be high enough cause some symptoms. The radiation must come from an external source such as high energy gamma-rays and penetrate to internal organs. The person’s entire body, or most of it, most be exposed acutely, that is, in a matter of seconds or minutes. Examples of people who suffered from acute radiation syndrome are the survivors of the Hiroshima and Nagasaki atomic bombs (image to the left contains a Japanese girl recovering from the effects of radiation sickness), the firefighters the first responded after the Chernobyl Nuclear Power Plant 1986 event, and some unintentional exposures to sterilization irradiators.
The main consequence of an acute radiation exposure is a decrease in life span of the exposed organism. The decrease in life span has a positive correlation with the dose of radiation exposure. Because there are high variations in survival times between different species and between animals within the same species, organism survival times are expressed as the average survival time which takes the many variations into consideration. A value known as the lethal dose is used to describe the relationship of survival of a whole population of the same species exposed to the same dose compared to the percentage of the population that will be killed from that same dose within a given period of time. To illustrate, the lethal dose required to kill fifty percent of a population in thirty days is expressed as LD 50/30. Table 4-1 lists the LD 50/30 doses in rads for several species.
For humans, a LD 50/60 is more useful since humans usually survive over thirty days of the radiation exposure. The LD 50/60 for humans is approximately 250-300 rads. The dose of radiation exposure has an inverse relationship with the survival time. A mammalian dose survival curve can be seen below; one can deduce the fact that as the radiation dose goes up, the survival time and number of survivors decreases.
In referring to the three regions of the mammalian dose survival curve above, there are three different systems that can result in death to the animal. Other organs and systems have suffered damage, but the principal cause of death is destruction to one specific system. The three defined acute radiation syndromes are named according to failure of that organ system which causes death: the bone marrow (hematologic) syndrome, the gastrointestinal syndrome, and the cardiovascular/central nervous system syndrome.
Depending on the absorbed dose, symptoms appear within hours to weeks, following a predictable clinical course. The signs and symptoms that develop in acute radiation syndrome occur through four distinct phases: prodromal phase, latent phase, manifest illness stage, and recovery of death phase. The prodromal phase of the acute radiation syndrome usually occurs in the first 48 hours may develop up to six days after initial exposure. The prodromal stage is also known as the N-V-D stage named after the classic symptoms of the stage: nausea, vomiting, as well as anorexia and possibly diarrhea depending on dose. After high radiation doses, additional symptoms such as prostration, fever, respiratory difficulties, and increased excitability may develop. This is the stage at which most victims seek medical care. The second stage, the latent stage, is the transitional period in which many of the initial symptoms resolve, and may last for up to 3 weeks depending on the original radiation dose. This time interval decreases as the initial dose increases. After the latent stage, the manifest illness stage is the period of time when overt illness develops, often characterized by infection, bleeding, electrolyte imbalance, diarrhea, changes in mental status, and shock. During this stage, the exposed organism will show signs and symptoms of the specific syndrome reflecting the organ system that is damaged. The manifest illness stage lasts from minutes to weeks depending on the dose. The last stage, the recovery or death phase, follows the period of overt illness, which may take weeks or months to resolve. The effected animal will either recover or die in this stage as a result of the damage sustained from the initial radiation exposure. These stages are described in further detail in the table below.
Acute Radiation Syndromes | Syndrome | Dose* | Prodromal Stage | Latent Stage | Manifest Illness Stage | Recovery | Hematopoietic
(Bone Marrow) | > 0.7 Gy (> 70 rads)
(mild symptoms may occur as low as 0.3 Gy or 30 rads) | • Symptoms are anorexia, nausea and vomiting.
• Onset occurs 1 hour to 2 days after exposure.
• Stage lasts for minutes to days. | • Stem cells in bone marrow are dying, although patient may appear and feel well.
• Stage lasts 1 to 6 weeks. | • Symptoms are anorexia, fever, and malaise.
• Drop in all blood cell counts occurs for several weeks.
• Primary cause of death is infection and hemorrhage.
• Survival decreases with increasing dose.
• Most deaths occur within a few months after exposure. | • in most cases, bone marrow cells will begin to repopulate the marrow.
• There should be full recovery for a large percentage of individuals from a few weeks up to two years after exposure.
• death may occur in some individuals at 1.2 Gy (120 rads).
• the LD50/60† is about 2.5 to 5 Gy (250 to 500 rads) | Gastrointestinal (GI) | > 10 Gy (> 1000 rads)
(some symptoms may occur as low as 6 Gy or 600 rads) | • Symptoms are anorexia, severe nausea, vomiting, cramps, and diarrhea.
• Onset occurs within a few hours after exposure.
• Stage lasts about 2 days. | • Stem cells in bone marrow and cells lining GI tract are dying, although patient may appear and feel well.
• Stage lasts less than 1 week. | • Symptoms are malaise, anorexia, severe diarrhea, fever, dehydration, and electrolyte imbalance.
• Death is due to infection, dehydration, and electrolyte imbalance.
• Death occurs within 2 weeks of exposure. | • the LD100‡ is about 10 Gy (1000 rads) | Cardiovascular (CV)/ Central Nervous System (CNS) | > 50 Gy (5000 rads)
(some symptoms may occur as low as 20 Gy or 2000 rads) | • Symptoms are extreme nervousness and confusion; severe nausea, vomiting, and watery diarrhea; loss of consciousness; and burning sensations of the skin.
• Onset occurs within minutes of exposure.
• Stage lasts for minutes to hours. | • Patient may return to partial functionality.
• Stage may last for hours but often is less. | • Symptoms are return of watery diarrhea, convulsions, and coma.
• Onset occurs 5 to 6 hours after exposure.
• Death occurs within 3 days of exposure. | • No recovery is expected. | * The absorbed doses quoted here are “gamma equivalent” values. Neutrons or protons generally produce the same effects as gamma, beta, or X-rays but at lower doses. If the patient has been exposed to neutrons or protons, consult radiation experts on how to interpret the dose.
† The LD50/60 is the dose necessary to kill 50% of the exposed population in 60 days.
‡ The LD100 is the dose necessary to kill 100% of the exposed population | |
The bone marrow syndrome, also referred to as the hematologic or hematopoietic syndrome, occurs between 100-1,000 R range, with death occurring within six to eight weeks in some individuals at a dose of 200 R. This syndrome is exhibited by destruction of bone marrow caused by a reduction of red and white blood cells and platelets resulting from radiation exposure. The bone marrow syndrome is characterized by anorexia (lack of appetite), fever, malaise, sepsis, and hemorrhagic complications. The hematopoietic system shows the earliest indication of the severity of the radiation exposure through the rapidity and degree of drop in the cell count which includes lymphocytes, granulocytes, thrombocytes, and reticulocytes. The reduction in cell count causes the symptoms associated with this syndrome. The absolute lymphocyte count at 48 hours after initial exposure is a good predictor for prognosis. To illustrate, if the total lymphocyte count is greater than 1,200 it is unlikely that the effected patient has received a lethal dose. If at 48 hours the lymphocyte cell count is between 300 and 1,200, a significant exposure has occurred and the patient should be hospitalized with barrier protection isolation. Lymphocyte levels of lass then 300 cell per/ml are usually critical and warrant the consideration of the use of colony-stimulating factors on an individual basis. For people suffering with this syndrome, survival time is dose dependent. In the range of 100-300 R, the bone marrow repopulates enough to sustain life in most individuals.
The gastrointestinal syndrome appears in all animals at doses between 1,000 and 10,000 range.
Symptoms in this system are regularly seen at a threshold dose of 600 rads and result from damage to the epithelial cells lining the intestinal tract. The higher the exposure, the sooner the symptoms of nausea and vomiting develop. The presence of these symptoms typically overlaps with the drop in the cell count described previously. As a result, sepsis, loss of fluids, electrolytes and opportunistic infections complicate the picture. Persistent high fevers and bloody diarrhea is an ominous sign despite fluid and electrolyte replacement. Survival time in this syndrome does not vary with dose. Death happens at the same time regardless of dose. Human death occurs within three to ten days without medical support and within approximately two weeks with medical …show more content…
intervention.
Central nervous system symptoms are seen with acute radiation doses in excess of 1000 rads and are probably due to diffuse microvascular leaks within the brain. Damage to these blood vessels result in the loss of fluids and electrolytes, edema, increased intracranial pressure, and death. This injury is irreversible and the victim rarely lives long enough to suffer any hematological or gastrointestinal symptoms. Symptoms of shock may develop quickly in these patients. The central nervous system syndrome occurs at doses greater than 5,000 rads in humans. Death is usually within hours, but may occur two to three days post-exposure. Depending on the dose, the prodromal stage lasts from a few minutes to a few hours. The person suffers nervousness, confusion, nausea and vomiting, a loss of consciousness, and burning sensations of the skin. A latent period may last several hours. Manifest illness occurs five to six hours after exposure, resulting in diarrhea, convulsions, coma, and death.
All organs and body tissues can be affected by partial body irradiation. The result is death to some of the cells, which results in atrophy or shrinking of the tissue or organ. Although recovery is possible, atrophy may lead to the effected organ or tissue becoming nonfunctional. With high enough doses, any local tissue will react. Tissue response depends on its radiosensitivity, reproduction, and maturation rates. Due to the early uses of radiation and radiation therapy, the effects of radiation on the skin are very well understood. Various skin changes occur depending on the radiation dose. The injuries tend to progress with dose level and there appears to be a threshold effect for these clinical signs. Early erythema, reddening of the skin, is an early indicator that someone has had too much radiation exposure. At doses around 300 rads, erythema will develop within a few hours, but more importantly, it can appear within a few hours only to reappear at a later time. Therefore, the effected person should be examined on an hourly basis for this sign and ideally photographs should be taken to document this sign. If local radiation dermatitis develops with this sign, the dose is in the region of 1,000 rads. If blistering occurs then the dose is in the range of 1,500 rads. Also, if necrosis develops, the dose is in the region of greater than 5,000 rads. Therefore, by noting these clinical signs, one is able to establish the approximate dose range the patient was subjected to and these doses would be confirmed by dosimetry at a later stage. The table below further describes radiation effects on the integumentary system.
The diagnosis of acute radiation syndrome in a patient without a confirmed history of acute exposure to ionizing radiation can be very difficult due to the nonspecific nature of symptoms. A complete blood count (CBC) should be collected at time of patient presentation and repeated regularly (every four hours for the first eight hours, then every six hours for the following 40-48 hours), and absolutely lymphocyte count should be measured. The table below illustrates lymphocyte depletion curves and accompanying clinical severity ranges.
An initially low or rapidly falling lymphocyte count is indicative of a high dose of radiation. Estimation of exposure is important as this information is needed to guide treatment decisions. Information about estimated radiation dose and hence severity of radiation illness can also be inferred on the basis of time to onset of vomiting, which is typically inversely related to absorbed dose, although at lower doses this information is less reliable. Onset of vomiting ranges from less than ten minutes at an estimated dose of 8 Gy ir higher, to greater than two hours at doses of less than 2 Gy. As emesis may be symptomatic of a range of other conditions, patients should also be assessed for the presence of other adverse health effects that would support a diagnosis of acute radiation syndrome. See the table below for an estimation of dose related to onset of vomiting for single acute exposure of radiation.
Cytogenetic dosimetry is the gold standard and only accurate method of determining radiation dosing. The test is based on predictable and standardized effects of radiation on the replication of deoxyribonucleic acid (DNA) in lymphocytes. However, cytogenetic dosimetry is not widely available and results take several days to process.
Patients with acute, high dose, whole body irradiation will fall into one of three categories: those who recover with minimal intervention; those who require aggressive supportive care, up to and including bone marrow stem cell transplants; and those who – due to the dose they received, concomitant physical trauma, or inadequate clinical resources – will be triaged to receive palliative care. Except for the moribund individual, patient management during the prodromal phase is fairly uniform, regardless of triage category. Obtaining a history and physical examination, removal of external contamination, dose estimation, supportive care (including psychological support of the patient and family), symptomatic treatment, and replacement of fluids and electrolytes should be the earliest goals of medical management. With the onset of the latent phase, medical staff should have at least a crude estimate of absorbed dose and illness severity. Individuals with hematopoietic syndrome should be transferred to tertiary care centers specializing in the care of pancytopenic patients. Physical trauma or burn injury superimposed on radiation exposure predisposes victims to a worse overall prognosis. Individuals with such combined injuries, along with those whose clinical picture suggests an even higher absorbed dose, should be provided with comfort care in order to alleviate pain and suffering.
Over the first week to 10 days postexposure – as granulocytes begin to decrease towards a nadir – it is critical to support neutrophil levels. As the number of neutrophils falls, the likelihood of infection increases. Patients most at risk are those with neutrophil counts <0.5 × 109cells/liter. Consultations with infectious disease specialists and hematologists are recommended if febrile neutropenia develops.2,12Strict infection control can and should be supplemented as soon as possible by administration of cytokines: granulocyte colony stimulating factor (G-CSF) or granulocyte-macrophage colony stimulating factor (GM-CSF). These drugs stimulate neutrophil precursor cells in the bone marrow to divide and produce mature cells. Subpopulations of radioresistant bone marrow stem cells unaffected by ionizing radiation and pools of hematopoietic stem cells spared by shielding provide an intrinsic reservoir for recovery, especially when enhanced by the use of cytokines and intensive supportive care.13
Neither G-CSF nor GM-CSF has been approved for use by the US Food and Drug Administration (FDA) as a treatment for radiation-induced neutropenia. Nevertheless, the “non-approved” use of G-CSF (filgrastim or Neupogen®), GM-CSF (Leukine®, Leucotropin®), or the pegylated form of G-CSF (peg-filgrastim or Neulasta®) has been recommended by the Strategic National Stockpile (SNS) Radiation Working Group and by other experts in radiation medicine.5 The Centers for Disease Control and Prevention (CDC), which has oversight for the SNS, currently holds an Investigational New Drug application with the FDA for the release and use of Neupogen® following a radiation mass casualty event. Bone marrow stem cell transplants can be considered for whole body absorbed doses of 700 to 1000 rad (7 to 10 Gy). The Radiation Injury Treatment Network (http://bloodcell.transplant.hrsa.gov/ABOUT/RITN/index.html) was developed to respond to potential disasters where victims may suffer overwhelming bone marrow damage.
The CDC has produced a broad range of educational products including fact sheets, satellite broadcasts, videos, and CD-ROMs (http://www.bt.cdc.gov/radiation/).
The Radiation Event Medical Management (REMM) web portal (http://remm.nlm.gov/), developed under the auspices of the US Department of Health and Human Services, includes guidance for health care providers. Finally, radiation emergency medicine consultation services are provided by the Radiation Emergency Assistance Center/Training Site (REAC/TS). REAC/TS physicians and health physicists are available 24 hours a day, 7 days a week at 865.576.1005 (http://orise.orau.gov/reacts/).
Health care providers may yet be called upon to provide care to victims of acute, high-dose, ionizing radiation exposure following a terrorist radiation event. ARS, a consequence of such an exposure, will be assessed and managed on the basis of a thorough history and physical examination, diagnostic testing, and appropriate resource allocation. Even with proper management, recovery from ARS takes a long time and lifelong medical follow up is
essential.