Ionizing Radiation Injuries and Illnesses: Ensuring Patient Safety and Self-Preservation
Authors: Erica Simon, DO, MHA (@E_M_Simon, EM Chief Resident at SAUSHEC, USAF) and Daniel Sessions, MD (EM Associate Program Director, SAUSHEC, USAF / Medical Toxicologist, South Texas Poison Center) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UT Southwestern Medical Center / Parkland Memorial Hospital)
It’s early in the afternoon on what has been a relatively uneventful shift in the emergency department (ED). As you finish suturing a hand laceration, the charge nurse enters the room to inform you of a phone call requiring your attention. As you saunter to the clerk’s desk, you lift the receiver to here a man’s shaking voice:
“Are you a doctor? My name is John Brown – I need to speak to a doctor. I’m a nuclear engineer. I work at the research laboratory in town. My project deals with enriched uranium and I was exposed to the material an hour ago. I went through the lab’s decontamination shower. I’m feeling nauseous, and I’ve vomited twice already. What do I do?”
If you’re hurriedly attempting to recall specifics regarding decontamination, evaluation, and treatment, read on. We’ll offer a quick review to ensure your patient’s safety, as well as your own.
Radiation injuries and illnesses are rare. Much of the information that we have gained stems from epidemiologic studies of nuclear incidents, two of which marked the history of the U.S.:
On August 6, 1945, “Little Boy,” a uranium gun-type device, was released from a B-29 Superfortress over the city of Hiroshima. Three days later, “Fat Man,” a plutonium implosive bomb detonated above Nagasaki. While reports vary, it is believed that by the end of 1945, these weapons, with their heat, physical force, and ionizing radiation, were responsible for the deaths of 90,000-120,000 residents of Hiroshima, and 60,000-80,000 inhabitants of Nagasaki.1-3
In addition to the atomic bombs, the Radiation Emergency Assistance Center/Training Site Radiation Accident Registries now reports 420 nuclear incidents as occurring between 1944-2011, perhaps the most notable being those in Goiânia, Chernobyl, and Fukushima:
During late 1985, individuals rummaging through an abandoned radiotherapy facility in Goiânia, Brazil, came across a Cesium-137 teletherapy unit. Thinking that the source capsule might be of value, the men attempted to disassemble it, exposing the cesium contents and releasing cesium chloride salt into the environment. The men then utilized the capsule contents to barter with families in the local area, exposing thousands to ionizing radiation. All told, the incident required the medical monitoring of 112,000 individuals.4
In April 1986, employees of the Chernobyl Power Complex, north of Kiev, Ukraine, began to perform an operational test of a nuclear reactor. As a number of the reactor’s safety mechanisms had been disabled, a steam explosion occurred, releasing fission products into the atmosphere. The compounds iodine-131 and cesium-137 delivered significant radiation doses to the surrounding populations. All told, 28 deaths were attributed to the incident, six on scene during the time of the event. To date, Chernobyl represents the largest uncontrolled nuclear incident recorded for any civilian operation.4
In March 2011, following a major earthquake, a tsunami disabled the power supply and cooling mechanisms of three nuclear reactors (designed with low-enriched uranium cores) in the Fukushima I Nuclear Reactor Power Plant, Japan.5 While there were no reported deaths or cases of radiation associated sickness, more than 100,000 individuals were evacuated from their homes given the risk of exposure.6
We’ll discuss long-term radiation-related health effects at a later point, but let’s start with the basics:
Radiation, Exposure, and Contamination
Medical sources and background radiation (environmental ionizing radiation – radon, thoron, etc.) represent the greatest contributors to ionizing radiation exposure for persons residing in the U.S.7 Today the largest man-made sources of ionizing radiation are diagnostic medical testing (radiation: CT > fluoroscopy > radiograph), and therapeutic irradiation (external beam radiation therapy utilizing gamma ray sources or x-ray machines).7
Radiation exposure is defined as being in the presence of ionizing radiation. Contamination occurs when radioactive materials are ingested, inhaled, percutaneously absorbed, or absorbed through breaks in the skin.8 Ionizing radiation is emitted in the form of alpha particles, beta particles, gamma rays, or xrays. Alpha particles are high mass, travel only a short range from their source, and are unable to penetrate the dermis. Beta particles are of lower mass as compared to alpha particles, travel several feet from their source, and are capable of penetration to the germinal layer of the dermal matrix.7 Alpha and beta particles are most commonly harmful when exposure involves ingestion or penetration of broken skin. Gamma rays and xrays are harmful, high energy, highly penetrating forms of radiation.1
The energy of ionizing radiation is measured in electron volts (eV) and may be expressed as kilo-electron volts (keV or 103 eV) and mega-electron volts (MeV or 106 eV). Table 1 (Christensen et al.’s 2014 publication8) details common radioactive materials and their use.
When radiation is deposited into matter it is referred to as the radiation absorbed dose or rad. The SI unit for absorbed dose is the gray (Gy). We’ll save the discussion of conversion from ergs (units of energy and work) and suffice it to say that 1Gy = 100 rads and 1 rad = 0.01 Gy.
How Much is Too Much?
Radiation type, respective linear energy transfer (LET – the average amount of energy lost per unit track length in tissue), total dose, dose rate, route of exposure, distribution of exposure, and distance from the source are important factors in determining the degree of radiation injury.7
Radiation Type and LET
Both gamma rays and xrays are low-LET (retaining energy while traveling through tissues – penetrating to a greater extent), thus primarily resulting in indirect biologic injury through the radiolysis of water molecules and the generation of free radicals. High-LET radiation (alpha and beta particles) are known to incite direct cellular injury, but demonstrate poor penetrance.7
Total Dose and Dose Rate
Dose rate refers to the amount of radiation absorbed over time.7 Exposure to a low-LET ionizing radiation (gamma rays or xrays) would require a higher total dose to achieve the same effect as irradiation of the same tissue at a high dose rate. For high-LET radiation (alpha and beta particles), the effect is independent of the dose rate.7
Let’s speak in grays:
Not all texts are in agreement: a number of sources site whole body radiation doses of 1-2 Gy and 2-6 Gy as inducing mild and median forms of acute radiation sickness (ARS) (treatable), and an exposure greater than 6 Gy commonly resulting in death (8-12 Gy exposure pre-disposing to death within 24 hours).9 In general, doses >1 Gy are considered “massive whole-body irradiation.” This amount represents 250 times the average annual dose of background (environmental) radiation in the US.
Numerous biologic and epidemiologic studies have focused on the carcinogenic dangers of alpha-emitting radioisotopes as they represent the largest environmental contributor to population exposure (environmental radon and radon decay products), and display a widespread presence in drinking water and indoor air.10 Today research has demonstrated that there is no minimum exposure threshold for radiation induced cancer, and that the risk of carcinogenesis increases with exposure in a non-linear fashion. However, as we’ll see shortly, ARS occurrence and severity can be predicted at specific threshold values.
Route of Exposure
As we touched on above, contamination occurs when radioactive materials are ingested, inhaled, percutaneously absorbed, or absorbed through breaks in the skin.8 Ingestion and inhalation are of primary importance in occupational and accidental situations, whereas percutaneous contamination is more commonly associated with military endeavors.7
Radioactive materials are frequently ingested as contaminants in food and water, and their absorption is a function of respective solubility. Direct radiation injury of the GI tract following ingestion is generally insignificant as the majority of the radiation from alpha and beta particles is absorbed and proliferating cells are protected by their location in intestinal crypts.7
With respect to inhalation, solubility is also an important factor. Soluble radioactive gases or particulates deposited into pulmonary tissues translocate from the lung to the blood stream and are disseminated throughout the body. Gases and particulates that are insoluble may remain in the lung for years depending upon the biological half-life.7
Distribution of Exposure
Distribution is critical when we discuss radiation injury. Only tissues that have been exposed to ionizing radiation display cellular damage.7
Distance from the Source
For point sources of radiation, the dose rate decreases as the square of the distance from the source (inverse square law).11
Signs and Symptoms of Acute Radiation Sickness
Let’s focus our attention on signs and symptoms following whole-body irradiation:
ARS in clinically divided into phases and syndromes:7,11
Prodromal Phase: Onset 0-2 days following exposure
Latent Phase: Onset 2-20 days following exposure
Manifest Illness: Onset 21-60 days following exposure
The prodromal phase is characterized by anorexia, apathy, nausea, emesis, diarrhea, fever, and headache. Onset of symptoms within 2 hours indicates potentially lethal exposures > 2 Gy.11
A prodrome is generally mild or absent if total body dose is ≤ 1 Gy. The latent period, during which the patient is symptom free, is usually of short duration (1-2 days) and is followed by overt illness characterized by the syndromes detailed below.
Cells most susceptible to radiation injury include those that are relatively undifferentiated and rapidly dividing: stem cells of the hematopoietic system, crypt cells of the intestine, spermatogonia, basal cells of the dermis, etc.7 Highly differentiated cells (skeletal muscle) or those that no longer possess the capability for replication (neurons) are relatively resistant to radiation injury. Bearing this in mind, our discussion of ARS syndromes is logically framed:
- Radiation Dose: 0.3-10 Gy, but predictably occurs at >1 Gy: destruction of erythroid and myeloid precursors resulting in leukopenia and thrombocytopenia.
- Mortality results from pancytopenia leading to sepsis. Gingival and gastrointestinal hemorrhage are common.
- Clinical Marker: Monitoring the decline in absolute lymphocyte count (ALC) is the most practical method of assessing radiation dose following exposure. Unlike RBCs and platelets, mature lymphocytes are rapidly destroyed by radiation-induced cell lysis. The rate of ALC decline and the nadir after exposure are a function of cumulative radiation dose. A 50% decline in the absolute lymphocyte count within the first 24 h after exposure, followed by a more severe decline within 48 h, characterizes a potentially fatal exposure in the range of 5–10 Gy.12 Lymphocyte nadir typically occurs 8-30 days after exposure.
- Most commonly develops within 5 days of exposure.
- Radiation Dose: < 1.5 Gy: prodromal symptoms detailed above: nausea and emesis.
- Radiation Dose: > 5 Gy: destruction of intestinal crypt cells and loss of mucosal barrier: abdominal pain, emesis, GI bleed.
- Mortality is related to dehydration, electrolyte imbalances, bacterial translocation (high fever and diarrhea), or bowel wall necrosis and subsequent perforation.
Cerebrovascular Syndrome (CNS Syndrome)11
- Radiation Dose: > 10 Gy
- Related to localized changes in the CNS: impaired capillary circulation, damage to the blood-brain barrier, interstitial edema, acute inflammation of the meninges, and petechial hemorrhages.13
- Patients may present with headache, nausea, altered mental status or may report a seizure.
- Physical exam: papilledema, ataxia, reduced or absent DTRs and corneal reflexes.
As an aside: a sampling of resources also discuss a cutaneous syndrome: developing 1-2 days following exposure and taking up to years to fully manifest (assuming survivability). Early lesions include erythema, edema, and desquamation. Advanced cases may be characterized by bullae, ulcerations, onycholisis, and necrosis.14
The Emergency Department Approach
If you are a healthcare provider responding to a nuclear accident, often times the incident command will disseminate a situation report detailing key factors which will allow for your preparation (e.g. – nuclear explosion: indirect blast and thermal injuries including ruptured TMs, burns, crush injuries, trauma secondary to flying debris, etc.).15
The majority of facilities publish protocols directing the provision of care in the case of nuclear exposure. If treating isolated cases, these documents are valuable tools as they commonly identify points of contact for local and state radiation agencies, local hazardous materials disposal and removal sites, and the US Department of Energy’s Radiological Assistance Program (Emergency Number: 865-576-1005).17 A toxicologist can also provide recommendations and should be consulted.
By federal law, hospitals that utilize radiologic materials are required to appoint a radiation safety officer.8 Contact this individual as he/she will be your greatest resource in terms of facility capabilities and supplies (dosimeters, etc.).
Addressing the Patient
The first step in offering aid to a victim involved in a nuclear incident is to protect yourself. Disposable scrubs with the seams taped, waterproof shoe covers, hats, masks, and goggles are a must. A dosimeter should be worn at all times (determines the type of radiation and total exposure).15
Decontamination should begin with the removal and packaging of contaminated clothing. Saline irrigation should be utilized for all open wounds. Cleansing of the dermis with mild soap (taking care not to excoriate the intact epithelial layer) should then be performed.15 Ideally this process is undertaken in cooperation with radiologic response personnel such that contamination levels are ascertained and the patient is cleared for further medical evaluation.
In an emergency response scenario, partnering with local experts is advised as total radiation dose estimation allows triage and targeted therapy (e.g. – patients experiencing a dose of > 10 Gy may be transitioned to palliative care). Reverse isolation is recommended for patients with an estimated whole-body irradiation dose of 2-3 Gy.16
Primary and secondary surveys should be performed on all trauma patients with interventions, resuscitative measures, and imaging performed as appropriate. It is recommended that all medically necessary surgical procedures be performed within 36 hours of exposure given the propensity for anemia, thrombocytobenia, immunosuppression, and GI bleeding in the hours following.17
For the stable patient, emergency department evaluation begins with an assessment of the ABCs. If possible, a thorough history and physical examination should be performed. When collecting HPI data, question specifically regarding ARS symptoms and their time of onset (anorexia, nausea, vomiting, bloody diarrhea, confusion, loss of consciousness or fever). The physical examination should focus on findings associated with ARS: papilledema, ataxia, focal neurologic findings (decreased DTRs), cutaneous skin lesions, petechiae (thrombocytopenia), abdominal tenderness to palpation.
- Blood, urine, and feces samples should be obtained from all contaminated patients and stored/processed/disposed of according to facility radiation sample guidelines.15
- Swab the nostrils, oral cavity, and all wounds to assess for the possibility of internal contamination.16
- Obtain a CBC with differential for all patient with radiation injury. (If possible, perform venipuncture at site free of contamination). For patients with whole-body irradiation, repeat the CBC q 4-8 hours, then q 24 hours.11
- Samples for chromosomal analysis may also be collected. Dicentric chromosomes correlate most reliably with radiation dose.11
- Patients with internal exposure require urine and feces collection with proper storage for 4 days duration.15
Supportive care and replacement of fluids and electrolytes are early goals of therapy. Odansetron and Granisetron may be administered for radiation-induced emesis.15,18 Sucralfate should be utilized for the prevention of stress ulcers (antacids and H2 blockers are to be avoided as maintenance of gastric acidity is recommended).15,19 Cytokine therapy advised immediately following exposure in individuals having been known to receive a whole-body irradiation dose of ≥ 2 Gy with mechanical trauma, children < 12 years of age, and the elderly in order to prevent hematopoietic syndrome.11,20
The management of hematopoietic syndrome is complex and should be performed in consultation with a hematologist as bone marrow transplant has been demonstrated to improve survival. Severe anemia and thrombocytopenia most commonly develop 2-4 weeks following exposure. If and when requiring a transfusion, patients known to have received > 1 Gy of irradiation should receive irradiated, leukoreduced blood products to prevent transfusion-associated graft-versus-host disease, febrile non-hemolytic reactions, and CMV infection.20 In irradiated patients with or without medical problems, platelets should be maintained at > 20,000/L (if surgery is required, > 75,000/L).11,20
Infection is a major concern following whole-body irradiation given cutaneous lesions, gut bacterial translocation, and immunosuppression (leukopenia, neutropenia). Neutropenia prophylaxis is recommended: a floroquinolone, an antiviral agent, and an antifungal agent.11 Broad-spectrum antibiotic therapy should be administered to febrile patients.11 Pneumocystis jiroveci prophylaxis should be initiated if CD4 < 200/uL.20
Iodine – In the setting of a radioactive iodine release (nuclear power plant or weapon), health officials may recommended the administration of potassium iodide.17 Potassium iodide saturates the iodine binding sites within the thyroid and inhibits incorporation of radio-iodines into the thyroid gland.21
Cesium and Thallium – Prussian Blue is an oral ion-exchange therapy which disrupts the entero-hepatic circulation of cesium and thallium, increasing their elimination through the GI tract.22,23
Plutonium, Americium, and Curium – Diethylenetriamine pentaacetate (DTPA) is a chelating agent, which may be utilized in the setting of plutonium, americium, and curium irradiation. In the U.S., DTPA is available in two forms: calcium DTPA (Ca-DTPA) and zinc DTPA (Zn-DTPA). Ca-DTPA is more effective than Zn-DTPA when given within the first 24 hours after contamination, after 24 hours Ca-DTPA and Zn-DTPA are equally as effective.24
Today we know that survival is inversely proportional to the ionizing radiation dose:17
- 20Gy – supralethal
- >10Gy – comfort care advised
- 5-10Gy – rapid onset, severe hematopoietic and gastrointestinal syndromes; survival with advanced care
- 2-5Gy – delayed onset, less severe symptoms
- <2Gy – survival expected with care
The following is not all-encompassing, but offers examples:
- Epidemiologic studies of Hiroshima and Nagasaki survivors have demonstrated an increase risk of carcinoma, specifically malignancies of solid organs (n= 100,000 subjects; 17,488 solid cancer incident cases identified, 853 estimated attributable to radiation (11% attributable fraction among survivors exposed to >0.005 Gy)).1
- A retrospective analysis of cataract procedures performed on the Hiroshima population demonstrated an excess risk of vision impairing opacities requiring surgical intervention at exposures > 1 Gy.25
- Radiation exposure is closely associated with heart disease. Dose-related alterations in lipid profiles suggest a mechanism linking radiation exposure to hepatosteatosis and ischemic heart disease.26 Patients with exposure >0.5 Gy demonstrated a linear dose response for heart disease morality (estimated relative risk 0.14).27
Back to our case:
The patient is a nuclear engineer who believes that he was exposed and contaminated by uranium at his facility. He has taken action through decontamination. What do we do next? Hopefully we are able to obtain additional information: Is there a radiation safety officer on call at his facility or a protocol in place for assistance in measuring and containing contamination?
We know that Mr. Brown is symptomatic within one hour of exposure suggesting the potential for a lethal dose. A phone call should be made to the hospital’s radiation safety officer, the toxicologist, and if need be the US Department of Energy’s Radiological Assistance Program to develop a plan for decontamination assessment and transport. Upon ED arrival, the patient should be placed in reverse isolation, labs should be obtained, fluid resuscitation and electrolyte repletion initiated, and ondansetron and sucralfate administered.
- Get help – the radiation safety officer/organizational protocols, and toxicologist should be able to provide information regarding instrumentation, resources for containment, and treatment.
- Protect yourself – always ensure appropriate PPE.
- Address the patient:
- Decontamination – remove clothing, irrigate all open wounds with saline, gently wash skin with mild soap.
- Trauma patient – surgery within the first 36 hours optimum.
- Stable patient with symptoms of ARS – treat nausea/emesis (ondansetron, granisetron), give sucralfate (stress ulcers), give CSF (≥ 2 Gy with mechanical trauma, children < 12 years of age, and the elderly), start neutropenia prophylaxis.
- Symptom onset within 2 hours of exposure => ASSUME LETHAL DOSE.
- Send labs:
- CBC, chromosome studies; start urine and feces collection if internal contamination.
- ALC: clinical marker of severity
- Transfusion Required:
- Irradiated, leukoreduced blood products
- Maintain platelets > 20,000 (>75,000 if surgery required).
- Iodine, cesium, thallium, plutonium, americium, or curium exposure: talk to the toxicologist for recommendations regarding therapy.
- Irradiated, leukoreduced blood products
- CBC, chromosome studies; start urine and feces collection if internal contamination.
References / Further Reading
- Douple E, Mabuchi K, Cullings H, Preston D, Kodama K, et al. Long-term radiation-related health effects in a unique human population: lessons learned from the atomic bomb survivors of Hiroshima and Nagasaki. Disaster Med Public Health Prep. 2011; 5(1): S122-S133.
- Ricks R. REAC/TS Registry of radiation accidents, 1944-2000. Oak Ridge: REAC/TS, 2001.
- Hiroshima and Nagasaki: The Physical, Medical, and Social Effects of the Atomic Bombings. New York: Basic Books; 1981. The Committee for the Compilation of Materials on Damage Caused by the Atomic Bombs in Hiroshima and Nagasaki.
- The Radiological Accident in Goiânia. International Atomic Energy Agency. 1988. Available from: http://www-pub.iaea.org/mtcd/publications/pdf/pub815_web.pdf
- Chernobyl Accident 1986. World Nuclear Association. 2016. Available from: http://www.world-nuclear.org/information-library/safety-and-shttp://www.world-nuclear.org
- Fukishima Accident. World Nuclear Association. 2017. Available from: http://www.world-nuclear.org/information-library/safety-and-shttp://www.world-nuclear.org/information-library
- Lombardini E, Pacheco-Thompson, Melanson M. Radiation and Other Physical Agents. In Hascheck and Rousseaux’s Handbook of Toxicologic Pathology. 3rd ed. Philadelphia, Elsevier Saunders. 2013; 44:1421-1503.
- Christensen D, Jenkins M, Sugarman S, Glassman E. Management of ionizing radiation injuries and illness, part 1: Physics, radiation protection, and radiation instrumentation. J Am Osteopath Assoc. 2014; 114(3): 189-199.
- Grammaticos P, Giannoula E, Fountos G. Acute radiation syndrome and chronic radiation syndrome. Hell J Nucl Med. 2013; 16(1): 56-59.
- Fabriant J, Bair W, Bender M, Borek C, Groer P, et al. National Research Council (US) Committee on the Biological Effects of Ionizing Radiations. Health risks of radon and other internally deposited alpha-emitters: Beir IV. Washington DC, National Academy Press. 1988.
- Lopez M, Martin M. Medical management of the acute radiation syndrome. Rep Pract Oncol Radiother. 2011; 16(4): 138-146.
- Goans R, Holloway E, Berger M. Early dose assessment in critical accidents. Health Phys. 2001; 81: 446.
- Fliedner T, Friescke I, Beyrer K, British Insitute of Radiology, editors. Medical management of radiation accident – manual on the acute radiation syndrome (METREPOL European Commission concerted action). British Institute of Radiology; Oxford 2001; 1-66.
- Peter R. Cutaneous radiation syndrome-clinical and therapeutic aspects. Radiat Protec Bull. 1996; 183:19.
- Skorga P, Persell D, Arangle P, Gilbert-Palmer D, Winters R, et al. Caring for victims of nuclear and radiological terrorism. Nurse Pract 2003; 28(2):24-31.
- Turai I, Veress K, Gunalp B, Souchkevitch G. Medical response to radiation incidents and radionuclear threats. BMJ. 2004; 328(7439): 568-572.
- Walker R, Cergeny R. Medical consequences of nuclear warfare. Office of the Surgeon General. 1989. Available from: http://www.afrri.usuhs.mil
- The Medical Aspects of Radiation Incidents. Radiation Emergency Assistance Center/Training Site. REACT/TS. 2010. Available from: http://www.orise.orau.gov/reacts.
- Donnelly E, Nemhauser J, Smith J. Acute radiation syndrome: assessment and management. South Med J. 2010; 103(6): 541-544.
- Radiation Injury Treatment Network. Acute Radiation Syndrome Treatment Guidelines. 2010. Available from: http://www.RTIN.net
- U.S. Food and Drug Administration. FDA Talking Paper: Guidance on Protection of Children and Adults against Thyroid Cancer in Case of Nuclear Accident. 2001. Available from: http://www.fda.gov/Drugs/EmergencyPreparedness/BioterrorismandDrugPreparedness/ucm063807.htm
- Centers or Disease Control and Prevention. Prussian Blue. 2016. Available from:https://emergency.cdc.gov/radiation/prussianblue.asp
- U.S. Food and Drug Administration. Questions and Answers on Prussian Blue. 2016. Available from: https://www.fda.gov/Drugs/EmergencyPreparedness/BioterrorismandDrugPreparedness/ucm130337.htm
- Centers or Disease Control and Prevention. DTPA (Diethylenetriamine pentaacetate). 2013. Available from: https://emergency.cdc.gov/radiation/dtpa.asp
- Neriishi K, Nakashime E, Minamoto A, et al. Postoperative cataract cases among atomic bomb survivors: radiation dose response and threshold. Radiat Res. 2007; 168(4): 404-408.
- Wong F, Yamada M, Sasaki H, Kodama K, Hosada Y. Effects of radiation on the longitudinal trends of total serum cholesterol levels in the atomic bomb survivors. Radiat Res. 1999; 151(6): 736-746.
- Shimizu Y, Kodama K, Nishi N et al. Radiation exposure and circulatory disease risk: Hiroshima and Nagasaki atomic bomb survivor data, 1950-2003. BMJ. 2010; 340:b5349.