Acute Radiation Syndrome 

Acute Radiation Syndrome – Urgent Action

• Preliminary decontamination (eg, remove clothing, bathe patient) is done before or during transport to medical facility
• Treat life-threatening injuries, even before assessing radiation exposure
• Potassium iodide given as soon as possible after exposure (within 6 hours) is indicated for thyroid protection when patient has been exposed to iodine radionuclides ⁵

11 Interesting Facts

1. Acute radiation syndrome is illness caused by irradiation of the whole body or a significant part of it by a high dose (usually more than 1 Gy) of penetrating radiation over a short time ¹
2. Includes several clinical syndromes (ie, cerebrovascular, gastrointestinal, and hematopoietic syndromes), each with a typical clinical course; syndromes may overlap ^2 3
3. Onset, manifestations, duration, and prognosis depend on dosage of radiation received ³
4. Early symptoms constitute a prodromal phase of radiation poisoning and typically include anorexia, nausea and vomiting, and diarrhea ¹
5. After a short period of improvement, patients develop symptoms of organ system–specific syndromes depending on radiation dose received ²
6. Patients exposed to high doses may only partially improve for up to a few hours before experiencing fatal decline characterized by cerebrovascular manifestations ¹
7. Radiation dose and clinical severity are determined according to time from radiation exposure to onset of vomiting, lymphocyte depletion kinetics (via serial CBC), and testing for chromosomal aberrations in lymphocytes ³
8. Cytokine therapy is the mainstay of treatment for radiation-induced myelosuppression; early initiation of treatment may reduce risk of developing hematopoietic syndrome ³
9. Other measures may include antimicrobial prophylaxis, stem cell transplant, and transfusions of RBCs and/or platelets
10. Specific treatment is not indicated when doses are less than 1 Gy or more than 10 Gy; doses between 10 and 12 Gy are universally fatal and patients should be offered comfort measures
11. Potassium iodide is indicated for thyroid protection in patients exposed to iodine radionuclides, such as in a nuclear power plant accident ⁴

Pitfalls

• Presence of trauma, burns, or other injuries can advance onset and increase duration of expected radiation symptoms

Terminology

Clinical Clarification

• Acute radiation syndrome is illness caused by irradiation of the whole body or a significant part of it by a high dose (usually more than 1 Gy) of penetrating radiation over a short time ¹
  • Also referred to as radiation poisoning, radiation toxicity, or radiation sickness
• Onset, manifestations, duration, and prognosis depend on dose of radiation received ³
  • Dose is quantified in grays (symbol: Gy), a unit of absorbed dose that reflects the amount of energy deposited into a mass of tissue (1 Gy = 1 J/kg)
    • 1 Gy = 100 rad (older terminology)
    • Effective dose, measured in sieverts (symbol: Sv), is calculated by multiplying actual organ doses by weighting factors based on their relative sensitivity to radiation and adding the sum ⁶
    • 1 Sv = 1 Gy (or 100 rad in older terminology) for x-rays (conversion depends on radiation type) ⁶
  • Lethal dose 50/60 (causing death in 50% of irradiated people within 60 days) is estimated to be 3.5 to 4 Gy in those without access to supportive care, and up to 7 to 9 Gy in those with rapid access to advanced medical care (ie, ICU, reverse isolation, and hematopoietic cell transplant) ³
    • Doses greater than 10 to 12 Gy are universally fatal ³
• Local radiation injuries (eg, involving hands) are common in the civilian sector where radiation devices are in industrial use; they may occur separately or coexist with acute radiation syndrome ⁷

Classification

• Acute radiation syndrome consists of several clinical syndromes, each with a typical clinical course; there may be overlap between syndromes ²³
  • Hematopoietic syndrome
    • Full hematopoietic syndrome occurs with doses exceeding 1 Gy; rarely clinically significant at exposures below this level ²
    • Many patients will recover; however, mortality increases with increasing dose ¹
    • Most deaths occur within a few months of exposure, primarily as result of infection and hemorrhage due to destruction of bone marrow ¹
  • Gastrointestinal syndrome
    • Full gastrointestinal syndrome occurs with doses over 10 Gy ¹
    • Survival is unlikely; death usually occurs within 2 weeks as result of irreparable destruction of gastrointestinal tract and bone marrow leading to infection, dehydration, and electrolyte imbalance ¹
  • Cerebrovascular (neurovascular) syndrome
    • Full cerebrovascular syndrome occurs with doses over 50 Gy; some symptoms occur with exposures as low as 20 Gy ^1 2
    • Death inevitably occurs within 3 days owing to circulatory collapse, cerebral edema, and raised intracranial pressure ¹
  • Cutaneous syndrome
    • Injury to skin and underlying tissue due to exposure to large external dose of radiation; may occur with or without acute radiation syndrome ¹
    • May result in permanent hair loss or skin damage at irradiated site
• Clinical course of acute radiation syndrome is described in the following 4 stages:
  • Prodromal stage
    • Symptoms such as nausea, vomiting, diarrhea, and headache occurring within minutes or up to several days following exposure ^1 3
  • Latent stage
    • Initial symptoms resolve after minutes to days and patient is asymptomatic for a period ranging from a few hours to a few weeks ¹
  • Manifest illness stage
    • Symptoms of specific form of syndrome develop and may last for hours to months ¹
  • Recovery or death
    • Patients who survive recover within several months; may take up to 2 years ¹
• Mechanism of radiation injury may be classified as follows: ⁶
  • External exposure
    • Patient is exposed to an external source of radiation (eg, radiation-producing machine, radioactive source) without necessarily having direct contact
    • Patient does not become radioactive and poses no hazard to others
  • Contamination
    • Patient may be externally contaminated with radioactive liquids, particles, or gases
    • Patient can become contaminated internally via ingestion, inhalation, absorption through skin, or penetration through open wounds
    • Care must be taken to avoid spreading radioactive material to other people and surroundings
  • Combined
    • Exposure with contamination
  • Any of above in conjunction with trauma or illness

Diagnosis

Clinical Presentation

History

• Prodromal stage
  • Onset of symptoms occurs earlier after exposure to higher doses
    • Occurs within minutes of exposure to doses exceeding 10 Gy ³
    • Typically begins between 2 and 6 hours after exposure to doses of 1 to 6 Gy ⁸
    • Prodromal symptoms may be mild or absent with doses under 1 Gy ³
  • Symptom duration increases with higher radiation dose ⁵
    • Duration may also increase in presence of trauma, burns, or other injuries ⁵
  • Symptoms may include any or all of the following: ¹
    • Anorexia
    • Nausea and vomiting
    • Diarrhea
    • Headache
    • Fever
    • Skin erythema or pruritus at site of localized exposure
  • Patients exposed to doses exceeding 20 Gy may present with additional symptoms associated with hypotension or central nervous system impairment ²
    • Confusion
    • Disorientation
    • Loss of balance
    • Loss of consciousness
• Latent stage
  • After a short period of improvement, patients develop symptoms of organ system–specific syndrome depending on radiation dose received ²
  • Patients exposed to high doses may improve only partially for up to a few hours before experiencing fatal decline characterized by cerebrovascular manifestations ¹
• Manifest illness stage
  • Hematopoietic syndrome⁵
    • Anorexia
    • Malaise
    • Fever
    • Fatigue
  • Gastrointestinal syndrome
    • Anorexia
    • Fever
    • Vomiting
    • Severe diarrhea
    • Crampy abdominal pain ⁵
    • Hematochezia ⁵
  • Cerebrovascular (neurovascular) syndrome
    • Watery diarrhea
    • Fever
    • Dyspnea
    • Seizures
    • Syncope
    • Blurred vision
    • Fatigue
    • Disequilibrium or lightheadedness
    • Coma
  • Cutaneous syndrome
    • Intense erythema and pruritus
    • Blistering
    • Ulceration

Physical examination

• Signs can include any or all of the following: ³⁹
  • Fever
  • Hypotension
  • Tachycardia
  • Tachypnea
  • Abdominal tenderness
  • Skin erythema or edema
  • Papilledema
  • Impaired level of consciousness
  • Motor/sensory deficits
  • Ataxia
  • Reduced or absent deep tendon reflexes
• Patients in latent phase may appear well ¹
• Cutaneous signs may develop over time and include the following: ⁹
  • Intense erythema ¹
  • Blistering ^1 9
  • Ulceration ¹
  • Bruising ⁹
  • Petechial hemorrhage ⁹
  • Ecchymoses ⁹
  • Desquamation ⁹
• Late signs of acute cutaneous exposure include hair loss, hypo- or hyperpigmentation, and skin atrophy or necrosis ¹

Causes

• Caused by irradiation of the whole body or a significant part of it by a high dose (usually over 1 Gy) of penetrating radiation over a short period
  • Radiation exposure can occur as result of external contamination with radioactive materials, or as a result of internal contamination via ingestion, inhalation, transdermal absorption, or penetration through open wounds; can occur alone or in combination ²
  • Radioactive materials deposited internally and fractionated doses (large doses delivered in small daily amounts) rarely produce acute radiation syndrome ¹
• Potential sources of high-dose ionizing radiation exposure include the following:
  • Major accident or attack at a nuclear industrial facility ¹⁰
  • Detonation of a nuclear weapon ¹⁰
  • Detonation of a dirty bomb (ie, conventional explosive device containing radioactive material) ¹⁰
  • Contamination with radioactive material ¹⁰
  • Entering irradiation chamber when source is unshielded

Risk factors and/or associations

Age

• Children and infants are more susceptible to acute radiation syndrome after a given radiation dose exposure ¹¹

Other risk factors/associations

• Severity of radiation injury is influenced by the following: ³
  • Dose of radiation
  • Dose rate (more damage from doses received over shorter period)
  • Distance from radiation source
  • Shielding
  • Type of radiation
  • Type and volume of tissue irradiated
  • Patient’s age and state of health
• Data suggest that smoking may decrease tolerance to ionizing radiation, thereby increasing risk of sequelae from a given radiation dose ^12 13

Diagnostic Procedures

• Lymphocyte depletion kinetics. – These lymphocyte depletion curves are called the “Andrews’ curves” and are named after an early radiation medicine pioneer, Gould Andrews MD.( Adapted from Andrews GA, Auxier Jr, Lushbaugh CC. The importance of dosimetry to the medical management of persons accidentally exposed to high levels of radiation. In: Personnel Dosimetry for Radiation Accidents. Vienna: International Atomic Energy Agency; 1965.)From Christensen DM et al: Ionizing Radiation Injuries and Illnesses. Emerg Med Clin North Am. 32(1):245-65, 2014, Figure 4.

Primary diagnostic tools

• Suspect acute radiation syndrome in patients with known or possible radiation exposure ¹⁴
  • Acute radiation syndrome requires the whole body or a significant part of it to be exposed to a high-dose, external source of penetrating radiation with the dose delivered over a short period (usually minutes)
• Determine whether patient has been exposed to external irradiation or contaminated with radioactive material, which will have additional implications for hospital management (eg, decontamination, radiation protection for personnel involved in care) ⁶
• Estimate radiation dose received using clinical and biologic markers ³
  • Time from radiation exposure to onset of vomiting
  • Lymphocyte depletion kinetics (via serial CBC)
  • Testing for chromosomal aberrations in lymphocytes
• Additional tests include the following:
  • RBC typing and measurement of serum electrolytes ³
  • Nasal and oral swabs to assess for radioactivity with Geiger counter or alpha-radiation detection device ³ if contamination with particulate radioactive material is suspected ⁶
  • Feces and urine collection to assess for radioactivity with Geiger counter or alpha-radiation detection device ³ if gastrointestinal or other internal contamination is suspected ⁶
  • CT or MRI of head to document presence of cerebral edema in patients with cerebrovascular syndrome ³
• Physical dosimetry with specific instruments can provide an estimate of individual radiation dose but is not usually practical in emergency department setting ³

An interactive algorithm for diagnosis and management of acute radiation syndrome ¹⁴is available from Radiation Emergency Medical Management at the United States Department of Health and Human Services

• This algorithm is based on the METREPOL scale (European Medical Treatment Protocols for radiation accident victims), which scores severity of radiation injury using clinical and biologic criteria to guide disposition and treatment decisions ¹⁵

Laboratory

CBC with differential

• Obtain baseline and repeat every 2 to 3 hours during initial 8 hours after exposure, then every 4 to 6 hours for the next 2 to 3 days ¹
• Pay particular attention to lymphocyte count to estimate radiation dose; rate of decline in absolute lymphocyte count reflects dose and clinical severity ⁷
• Chromosomal analysis cytogenetic bioassay
  • Used on lymphocytes from peripheral blood sample taken 24 hours after radiation exposure event ³
  • Frequency of chromosomal aberrations correlates to radiation dose ³
• RBC typing ¹⁵
  • Indicated in all patients with suspected acute radiation syndrome to prepare for any needed transfusion

Other diagnostic tools

• METREPOL score ³¹⁵
  • Protocol after a radiologic accident for triage and management of large groups of people
  • Primary score within first 48 hours guides disposition; 48 hours afterwards, repeat scoring guides subsequent therapy
  • Patients are scored on the following clinical and biologic criteria, with + being a grading of severity:
    • Score 1
      • Average delay before symptoms appear is less than 12 hours
      • Cutaneous erythema: 0
      • Asthenia +
      • Nausea +
      • Vomiting per 24 hours: maximum 1
      • Diarrhea/number of stools per 24 hours: maximum 2 to 3; bulky
      • Abdominal pain: minimal
      • Headache: 0
      • Temperature lower than 38 °C
      • Blood pressure: normal
      • No loss of consciousness
      • Blood lymphocyte count
        • At 24 hours: more than 1500 cells/μL
        • At 48 hours: more than 1500 cells/μL
    • Score 2
      • Average delay before symptoms appear is less than 5 hours
      • Cutaneous erythema: with or without
      • Asthenia ++
      • Nausea +++
      • Vomiting per 24 hours: 1 to 10
      • Diarrhea/number of stools per 24 hours: 2 to 9; soft
      • Abdominal pain: intense
      • Headache ++
      • Temperature 38 °C to 40 °C
      • Blood pressure: normal or temporary decrease
      • No loss of consciousness
      • Blood lymphocyte count
        • At 24 hours: 500 to 1500 cells/μL
        • At 48 hours: 100 to 1500 cells/μL
    • Score 3
      • Average delay before symptoms appear is less than 30 minutes
      • Cutaneous erythema: +++; before 3 hours
      • Asthenia +++
      • Nausea ++++
      • Vomiting per 24 hours: more than 10 times, intractable
      • Diarrhea/number of stools per 24 hours: more than 10, watery
      • Abdominal pain: excruciating
      • Headache: excruciating; signs of intracranial hypertension
      • Temperature: over 40 °C
      • Blood pressure: systolic under 80 mm Hg
      • May or may not be comatose
      • Blood lymphocyte count
        • At 24 hours: less than 500 cells/μL
        • At 48 hours: less than 100 cells/μL

Differential Diagnosis

Most common

• Bacterial gastroenteritis¹⁶
  • Inflammation of gastrointestinal tract caused by bacterial infection or bacterial toxins
  • As with radiation toxicity, can present with severe nausea, emesis, diarrhea, abdominal pain, malaise, hypotension, and/or headache
  • Can present in multiple victims in cases of outbreak (eg, cholera), just as acute radiation syndrome can present in a mass-casualty situation
  • Unlike with radiation toxicity, patient does not have known radiation exposure
    • WBC count can be normal or elevated and platelet count is normal (decreased in acute radiation syndrome)
    • WBCs can be present in stool
  • Differentiated on basis of history and laboratory findings; diagnosis can be confirmed by culture of causative organism
• Ricin poisoning ¹⁷
  • Toxicity due to ricin toxin, derived from castor beans, produced by the plant Ricinus communis
  • As with radiation toxicity, can present with abdominal cramping, diarrhea, and blood in stool when exposure is via oral ingestion, and can progress to hypotension and multiorgan failure
  • Unlike with most cases of radiation toxicity, exposure may be occult
    • Hematuria may be present and WBC level may be elevated (2- to 5-fold higher than normal)
  • Diagnosis is based on history of suspected exposure combined with laboratory evidence of metabolic acidosis, elevated hepatic enzymes, and abnormal renal function
    • Government laboratories can provide testing of environmental samples when there is suspicion of ricin poisoning

Treatment Goals

• Decontaminate patient and surroundings if radiation contamination has occurred; minimize exposure to health care personnel ⁸
• Treat any associated life-threatening injuries ⁶
• Provide supportive care to mitigate gastrointestinal, hematopoietic, and neurologic effects ³
• Prevent and treat infection
• Immediate treatment is not indicated with exposures less than 1 Gy, and treatment is palliative with exposures exceeding 10 Gy

Disposition

Admission criteria

Hospital admission is indicated for the following:

• Patients with a METREPOL primary score of 2 or 3 ³
• Patients whose laboratory values indicate hematopoietic syndrome degree 2, 3, or 4 ⁵
• Patients who are symptomatic or received an initial dose of more than 1 Sv ⁶

Criteria for ICU admission

• Hematopoietic syndrome degree 3 or 4 ⁵
• Reverse isolation is required for patients who received whole-body doses of 2 to 3 Gy ³

Recommendations for specialist referral

• Manage patients with suspected radiation poisoning in consultation with the following specialists: ³
  • Radiotherapist, radiation oncologist, health physicist, or nuclear medicine physician (due to knowledge of radiation and its effects)
  • Hematologist
  • Medical toxicologist
  • Depending on the situation, trauma surgeon, burn specialist, dermatologist, and/or neurologist may be consulted ⁵

Treatment Options

Preliminary decontamination (eg, remove clothing, bathe patient) is done before or during transport to medical facility

Treat life-threatening injuries, even before assessing radiation exposure

Initiate supportive care in a clean environment (eg, burn unit), including the following: ²

• Fluid and electrolyte replacement
• Pain management and comfort measures
• Antiemetics
• Antidiarrheal agents
• Psychosocial support

Specific countermeasures may be indicated in cases of internal contamination with certain radioisotopes; consult with radiation experts before administration

• Oral potassium iodide is indicated for thyroid protection after exposure to iodine radionuclides ⁴
  • Potassium iodide given as soon as possible after exposure (within 6 hours) is indicated for thyroid protection when patient has been exposed to iodine radionuclides ⁵
  • Blocks radioactive iodine from entering thyroid if given early enough after exposure to radioactive material to saturate thyroid tissue; the sooner a person takes potassium iodide, the more time the thyroid will have to “fill up” with stable iodine ⁴
• Oral ferric hexacyanoferrate (Prussian blue) is indicated in cases of internal contamination with radioactive cesium or thallium ⁴
  • Reduces absorption by trapping radioactive isotopes in the intestine; these isotopes are then excreted in stool
• IV calcium- or zinc-diethylenetriamine-pentaacetate is indicated for internal contamination with plutonium, americium, or curium ⁴
  • Radioisotopes bind to diethylenetriamine-pentaacetate and are excreted in urine
  • Most effective when administered shortly after contamination occurs; when given within 24 hours, calcium-diethylenetriamine-pentaacetate is recommended; after 24 hours, both agents are equally effective

Consult with hematologist and radiation expert regarding prognosis, cytokine therapy, stem-cell transfusion, and other aspects of management ⁷

Cytokine therapy is the mainstay of treatment for radiation-induced myelosuppression; early initiation of treatment may reduce risk of developing hematopoietic syndrome ³

• Indications include:
  • Adults with whole-body or significant partial-body radiation exposure over 3 Gy (according to biodosimetry) or clinical diagnosis of level 3 or 4 hematopoietic syndrome ²
  • Children aged younger than 12 years, adults aged older than 60 years, or those with major trauma or burn and whole-body or significant partial-body radiation exposure over 2 Gy ²
  • METREPOL score of 2 or 3 after 48 hours ³
• Short-term therapy may be appropriate when dose is relatively low (less than 3 Gy); prolonged therapy may be required when dose is high (exceeding 7 Gy) or traumatic injury or burns are present ²
• Any of the following hematopoietic stimulators may be used: ³
  • Granulocyte colony-stimulating factor (filgrastim)
  • Pegylated granulocyte colony-stimulating factor (pegfilgrastim)
  • Granulocyte-macrophage colony-stimulating factor (sargramostim)
  • Keratinocyte growth factor (encoded by the FGF7 gene)

Transfusion of packed RBCs and/or platelets is indicated for patients with severe anemia or thrombocytopenia (usually after 2-4 weeks) ²

• All products are irradiated to prevent transfusion-associated graft-versus-host disease and leukoreduced to reduce risk of febrile reactions, platelet alloimmunization, or cytomegalovirus infection ³

Antibiotic prophylaxis is indicated in patients with neutropenia ³

• Start treatment with a fluoroquinolone antibiotic (eg, levofloxacin) plus an antiviral (eg, acyclovir) and an antifungal (eg, fluconazole)
• If neutropenic fever develops, initiate broad-spectrum antibiotics
• If serologic evidence of cytomegalovirus reactivation appears, treat with ganciclovir or valganciclovir ³
• Initiate Pneumocystis carinii prophylaxis if CD4 lymphocyte count is less than 200 cells/μL (measured at 1 month then every 3-6 months postexposure until more than 200 cells/μL) ³

Hematopoietic stem cell transplant is warranted in a small fraction of patients: those who are capable of making a recovery but who have received a radiation dose so high that there is no potential for endogenous hematopoietic recovery ³

• Criteria include severe aplasia that persists after cytokine therapy for 14 to 21 days, with no residual hematopoiesis and no irreversible organ damage ³
• Nonurgent; observe patients for 14 to 21 days before administering
• Graft may be bone marrow, peripheral blood hematopoietic stem cells, or cord blood ³

Drug therapy

• Cytokines ³
  • Granulocyte colony-stimulating factor (filgrastim) ²
    • Filgrastim (E. coli) Solution for injection; Adults: 10 mcg/kg/day as a subcutaneous injection. Start therapy as soon as possible after a patient received or is suspected of receiving a radiation dose greater than 2 gray (Gy). Advise patients that efficacy for this indication was based on animal data (monkeys). Obtain a CBC panel prior to starting filgrastim (if access to laboratory testing is readily available) and then every 3 days during filgrastim therapy. Discontinue when the ANC is more than 1,000 cells/mm3 for 3 consecutive days or the ANC is more than 10,000 cells/mm3 after a radiation-induced nadir.
  • Granulocyte-macrophage colony-stimulating factor (sargramostim) ²
    • Sargramostim Solution for injection; Adults: 7 mcg/kg/day as a subcutaneous injection (patients weighing greater than 40 kg). Start therapy as soon as possible after a patient received or is suspected of receiving a radiation dose greater than 2 gray. Obtain a complete blood cell count panel prior to starting sargramostim (if access to laboratory testing is readily available) and then every 3 days during therapy. Discontinue therapy when the absolute neutrophil count (ANC) is greater than 1,000 cells/mm3 for 3 consecutive days or the ANC is greater than 10,000 cells/mm3 after a radiation-induced nadir.
  • Pegylated granulocyte colony-stimulating factor (pegfilgrastim) ²
    • Pegfilgrastim (E. coli) Solution for injection; Neonates and Infants weighing less than 10 kg: 0.1 mg/kg subcutaneously once, followed by a second dose of 0.1 mg/kg subcutaneously 1 week later (total of 2 doses). Give the first dose as soon as possible after suspected or confirmed exposure to radiation levels greater than 2 gray (Gy). Do not delay administration of pegfilgrastim if a CBC is not readily available; estimate a patient’s level of radiation exposure based on information from public health authorities, biodosimetry if available, or clinical findings such as time to onset of vomiting or lymphocyte depletion kinetics.
    • Pegfilgrastim (E. coli) Solution for injection; Infants and Children weighing 10 to 20 kg: 1.5 mg subcutaneously once, followed by a second dose of 1.5 mg subcutaneously 1 week later (total of 2 doses). Give the first dose as soon as possible after suspected or confirmed exposure to radiation levels greater than 2 gray (Gy). Do not delay administration if a CBC is not readily available; estimate a patient’s level of radiation exposure based on information from public health authorities, biodosimetry if available, or clinical findings such as time to onset of vomiting or lymphocyte depletion kinetics.
    • Pegfilgrastim (E. coli) Solution for injection; Children and Adolescents weighing 21 to 30 kg: 2.5 mg subcutaneously once, followed by a second dose of 2.5 mg subcutaneously 1 week late (total of 2 doses). Give the first dose as soon as possible after suspected or confirmed exposure to radiation levels greater than 2 gray (Gy). Do not delay administration if a CBC is not readily available; estimate a patient’s level of radiation exposure based on information from public health authorities, biodosimetry if available, or clinical findings such as time to onset of vomiting or lymphocyte depletion kinetics.
    • Pegfilgrastim (E. coli) Solution for injection; Children and Adolescents weighing 31 to 44 kg: 4 mg subcutaneously once, followed by a second dose of 4 mg subcutaneously 1 week later (total of 2 doses). Give the first dose as soon as possible after suspected or confirmed exposure to radiation levels greater than 2 gray (Gy). Do not delay administration if a CBC is not readily available; estimate a patient’s level of radiation exposure based on information from public health authorities, biodosimetry if available, or clinical findings such as time to onset of vomiting or lymphocyte depletion kinetics.
    • Pegfilgrastim (E. coli) Solution for injection; Adults, Adolescents, and Children weighing 45 kg or more: 6 mg subcutaneously once, followed by a second dose of 6 mg subcutaneously 1 week later (total of 2 doses). Give the first dose as soon as possible after suspected or confirmed exposure to radiation levels greater than 2 gray (Gy). Do not delay administration if a CBC is not readily available; estimate the level of radiation exposure based on information from public health authorities, biodosimetry if available, or clinical findings such as time to onset of vomiting or lymphocyte depletion kinetics.
• Potassium iodide ⁵
  • Daily treatment should continue (EXCEPT for infants less than 2 months of age and pregnant or lactating females) until public officials have determined it is safe to discontinue therapy. In general, daily dosing should continue until the risk of exposure has passed or until other adjunctive measures (eg, evacuation, sheltering, and control of the food and milk supply) have been successfully implemented. The FDA emphasizes that the overall benefits of potassium iodide far exceed the risk of overdosing in this situation.
    • Potassium Iodide Oral solution; Neonates and Infants through 1 month of age: 16.25 mg PO once. Consult with a healthcare provider before giving repeated doses. The FDA has specifically recommended that newborns be given priority with regard to adjunctive measures (like evacuation) in order to obviate the need for repeat dosing with potassium iodide.
    • Potassium Iodide Oral solution; Infants and Children age 2 months to 3 years: 32.5 mg PO once daily.
    • Potassium Iodide Oral solution; Children 4 to 12 years: 65 mg PO once daily.
    • Potassium Iodide Oral solution; Adolescents who weigh at least 70 kg (150 pounds): 130 mg PO once daily.
    • Potassium Iodide Oral solution; Adolescents weighing less than 70 kg (150 pounds): 65 mg PO once daily.
    • Potassium Iodide Oral solution; Adults: 130 mg PO once daily.
    • Potassium Iodide Oral solution; Pregnant or Lactating females: 130 mg PO once. Consult with a healthcare provider before taking repeated doses.
• Ferric hexacyanoferrate (Prussian blue)
  • Prussian Blue Oral capsule; Children 2 to 12 years: 1 g PO 3 times daily. Duration based on radioactivity measurements in urine and feces; usually treatment is for 30 days or longer.
  • Prussian Blue Oral capsule; Adults and Adolescents: 3 g PO 3 times daily. Duration based on radioactivity measurements in urine/feces; usually treatment is for 30 days or longer.
• Chelating agents
  • Ca-DTPA is preferred, if available, as the initial dose during the first 24 hours of internal contamination, as Ca-DTPA is more effective than Zn-DTPA during this period. After the first 24 hours of treatment, Zn DTPA and Ca-DTPA are equally effective at decontamination.
  • After the initial dose of Ca-DTPA, on the next day, if additional chelation therapy is necessary, it is preferable to switch to Zn-DTPA, if available, because of the safety concerns associated with prolonged Ca-DTPA use. If Zn-DTPA is not available, treatment may continue with Ca-DTPA; however, mineral supplements containing zinc should be given concomitantly as appropriate.
  • The duration of chelation treatment depends on the amount of internal contamination and individual response to treatment.
  • Pentetate calcium trisodium
    • Initial Dose
      • Pentetate calcium trisodium (Ca-DTPA) Solution for injection; Children younger than 12 years: 14 mg/kg IV, not to exceed 1 g.
      • Pentetate calcium trisodium (Ca-DTPA) Solution for injection; Adults: 1 g IV.
    • Maintenance dose (if required and Zn-DTPA unavailable)
      • Pentetate calcium trisodium (Ca-DTPA) Solution for injection; Children younger than 12 years: 14 mg/kg IV once daily. Max: 1 g per day.
      • Pentetate calcium trisodium (Ca-DTPA) Solution for injection; Adults and Adolescents: 1 g IV once daily.
  • Pentetate zinc trisodium
    • Initial Dose (if Ca-DTPA unavailable)
      • Pentetate zinc trisodium Solution for injection; Children younger than 12 years: 14 mg/kg IV once, not to exceed 1 g.
      • Pentetate zinc trisodium Solution for injection; Adults, Adolescents, and Children 12 years and older: 1 g once via IV push over 3 to 4 minutes or as an IV infusion over 30 minutes.
    • Maintenance dose (if required)
      • Pentetate zinc trisodium Solution for injection; Children younger than 12 years: 14 mg/kg IV once daily. Max: 1 g per day.
      • Pentetate zinc trisodium Solution for injection; Adults, Adolescents, and Children 12 years and older: 1 g once daily via IV push over 3 to 4 minutes or as an IV infusion over 30 minutes.
  • In adults, Zn DTPA and Ca-DTPA may be given via nebulization (1:1 ratio with saline or sterile water) if the contamination occurs ONLY by inhalation. Safety and effectiveness have not been established in the pediatric population.
• Antimicrobial prophylaxis
  • Fluoroquinolone antibiotic
    • Levofloxacin ³
      • Levofloxacin Solution for injection; Adults: 750 mg IV every 24 hours for 7 days.
  • Antiviral agent
    • Acyclovir ³
      • Acyclovir Sodium Solution for injection; Adults: 500 mg/m2/dose IV every 8 hours during period of risk has been used.
  • Antifungal agent
    • Fluconazole ³
      • Fluconazole, Dextrose Solution for injection; Adults: 400 mg IV once daily during high-risk period.

Nondrug and supportive care

Fluid and electrolyte replacement

Pain management and comfort measures

Antiemetics

Antidiarrheal agents

Psychosocial support

Comorbidities

• Any of the following injuries can exist alongside radiation injury due to a nuclear explosion or from detonation of a dirty bomb (ie, a conventional explosive device containing radioactive material), potentially influencing triage and individual treatment priorities: ⁵
  • Fractures
  • Lacerations
  • Hemorrhage
  • Rupture of viscera
  • Pulmonary edema
  • Barotrauma and its complications, including pneumothorax and arterial gas emboli
  • Flash burns, flame burns, flash blindness, and retinal burns due to thermal energy
• Presence of trauma, burns, or other injuries can advance onset and increase duration of expected radiation symptoms

Special populations

• Pregnant women ²
  • Consult with maternal-fetal medicine specialist and health physicist to assess risk to fetus
  • Supportive care is same as for patients who are not pregnant
  • Cytokines are pregnancy class C agents
  • Thyroid protection with potassium iodide is critical for mother and fetus if exposure to radioiodine has occurred

Monitoring

• Monitor patients without symptoms after exposure to 1 Gy or more, and those who survive acute radiation syndrome, with weekly or twice-weekly CBC for 4 to 6 weeks to document their WBC nadir and recovery

Complications

• Presence of trauma, burns, or other injuries can advance onset and increase duration of expected radiation symptoms
• Early complications
  • Fluid and electrolyte imbalance ⁵
  • Hemorrhage
  • Infection and sepsis⁵
  • Multiorgan failure
• Late sequelae
  • Radiation-induced pulmonary disease ³
    • Doses to lungs in excess of 8 to 10 Gy may result in acute radiation pneumonitis or fibrosis of lung
  • Embryonic/fetal effects ³
    • Growth retardation, gross congenital malformations, and microcephaly may occur with uterine doses over 0.5 Gy
    • Highest risk of mental retardation is irradiation of the fetus during the period of major neuronal migration (8-15 weeks), and incidence is dose-dependent
  • Radiation-induced malignancies ⁸
    • Leukemia ³
      • Risk is particularly increased after childhood exposure
      • Latency period is 2 to 5 years after exposure ³
    • Solid cancers
      • Latency period is 20 to 30 years after exposure ⁸
      • The strongest association is documented with papillary thyroid cancer; a dramatic increase is seen in people exposed to radiation in childhood and adolescence ³
  • Radiation-induced cardiovascular disease ¹⁸
    • Myocardial fibrosis and cardiomyopathy
    • Coronary artery disease
    • Arrhythmias
    • Pericardial disease
    • Valvular disease

Prognosis

• Prognosis depends on whole-body ionizing radiation dose received ⁸
  • 1 to 2 Gy: treatable and patients tend to recover
  • 2 to 6 Gy: treatable and recovery is possible
  • 6 to 8 Gy: often not treatable; thus, fatal outcome is likely
  • Greater than 8 Gy: generally not treatable; virtually no chance of survival following total-body exposure in excess of 10 to 12 Gy
• METREPOL radiation accident severity scoring predicts prognosis as follows: ³
  • Score 1: patients will survive
  • Score 2: patients may survive with maximum medical attention
  • Score 3: radiation-induced multiorgan failure is likely, and chances of survival are slim
• Children have an increased lifetime risk of developing the following long-term sequelae of radiation poisoning: ¹¹
  • Leukemia
  • Thyroid cancer
  • Breast cancer
  • Primary brain malignancy
• However, evidence is mounting that the risk of long-term effects, notably cancer, may be less than previously thought ¹⁹
  • The long-held linear no-threshold model of radiation long-term risk has come into question in recent years ²⁰
  • Exposures less than 100 mSv probably do not pose long-term risk, and long-term low-dose radiation may even be protective ^20 21

References

1.CDC: Acute Radiation Syndrome: A Fact Sheet for Clinicians. CDC website. Reviewed April 4, 2018. Accessed March 2, 2021. https://www.emergency.cdc.gov/radiation/arsphysicianfactsheet.asp

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2.Waselenko JK et al: Medical management of the acute radiation syndrome: recommendations of the Strategic National Stockpile Radiation Working Group. Ann Intern Med. 140(12):1037-51, 2004

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3.López M et al: Medical management of the acute radiation syndrome. Rep Pract Oncol Radiother. 16(4):138-46, 2011

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4.CDC: Radiation Emergencies. Medical Countermeasures (Treatments) for Radiation Exposure and Contamination. CDC website. Reviewed April 4, 2018. Accessed March 2, 2021. https://www.cdc.gov/nceh/radiation/emergencies/countermeasures.htm

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5.Dainiak N et al: The hematologist and radiation casualties. Hematology Am Soc Hematol Educ Program. 473-96, 2003

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6.American College of Radiology Disaster Planning Task Force: Disaster Preparedness for Radiology Professionals: Response to Radiological Terrorism. A Primer for Radiologists, Radiation Oncologists and Medical Physicists. Government Version 3.0. ACR website. Published 2006. Accessed March 2, 2021. https://www.acr.org/-/media/ACR/Files/Legal-and-Business-Practices/Disaster-Preparedness/Disaster-Preparedness-for-Radiology-Professionals.pdf

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7.Radiation Emergency Assistance Center/Training Site: The Medical Aspects of Radiation Incidents. 4th ed. REAC/TS website. Revised July 2017. Accessed March 2, 2021. https://orise.orau.gov/resources/reacts/documents/medical-aspects-of-radiation-incidents.pdf

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8.Grammaticos P et al: Acute radiation syndrome and chronic radiation syndrome. Hell J Nucl Med. 16(1):56-9, 2013

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9.Radiation Emergency Medical Management, National Library of Medicine, US Department of Health and Human Services: Guidance on Diagnosis and Treatment for Healthcare Providers: Targeted Physical Examination Following a Nuclear Detonation. REMM website. Updated March 10, 2021. Accessed March 29, 2021. https://www.remm.nlm.gov/physicalexam.htm

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10.Donnelly EH et al: Acute radiation syndrome: assessment and management. South Med J. 103(6):541-6, 2010

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11.WHO: Children and Radiation: Children’s Health and the Environment WHO Training Package for the Health Sector. Slide set. WHO website. Updated December 2009. Accessed March 2, 2021. http://www.who.int/ceh/capacity/radiation.pdf

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12.Neugut AI et al: Increased risk of lung cancer after breast cancer radiation therapy in cigarette smokers. Cancer. 73(6):1615-20, 1994

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13.Flint-Richter P et al: Possible interaction between ionizing radiation, smoking, and gender in the causation of meningioma. Neuro Oncol. 13(3):345-52, 2011

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14.Radiation Emergency Medical Management, National Library of Medicine, US Department of Health and Human Services: Guidance on Diagnosis and Treatment for Healthcare Providers. Choose Appropriate Algorithm: Evaluate for Contamination and/or Exposure. REMM website. Updated March 10, 2021. Accessed March 29, 2021. https://www.remm.nlm.gov/newptinteract.htm#skip

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15.IGorin NC et al: Consensus conference on European preparedness for haematological and other medical management of mass radiation accidents. Ann Hematol. 85(10):671-9, 2006

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16.Graves NS: Acute gastroenteritis. Prim Care. 40(3):727-41, 2013

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17.Pincus SH et al: Passive and active vaccination strategies to prevent ricin poisoning. Toxins (Basel). 3(9):1163-84, 2011

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18.Taunk NK et al: Radiation-induced heart disease: pathologic abnormalities and putative mechanisms. Front Oncol. 5:39, 2015

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19.Sutou S: A message to Fukushima: nothing to fear but fear itself. Genes Environ. 38:12, 2016

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20.Seong KM et al: Is the linear no-threshold dose-response paradigm still necessary for the assessment of health effects of low dose radiation? J Korean Med Sci. 31(suppl 1):S10-23, 2016

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21.Scott BR et al: Sparsely ionizing diagnostic and natural background radiations are likely preventing cancer and other genomic-instability-associated diseases. Dose Response. 5(3):230-55, 2006

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