You are in the last hour of a mostly quiet overnight shift in a small hospital in an even smaller town in the southwestern United States when an 11-year-old boy comes in with five episodes of emesis with nausea. He tells you that about 12 hours earlier he was exploring in the desert when he came across a group of metal containers sticking partially out of the desert floor.
He figured that they looked suitable for target practice with his pellet gun because they were old and rusty. After a few shots, he went up to the container to check his aim and noticed a liquid seeping from the bullet holes. Not thinking much of it, he decided to go home because the sun was setting. All was normal until about 4 a.m. when he woke up with uncontrollable vomiting. What are your next steps in caring for this patient?
Acute radiation syndrome (ARS) is defined by the Centers for Disease Control and Prevention as an acute illness caused by a radiation dose that is “large, external, and penetrates a significant portion of the body over a short period of time”. (April 4, 2018; http://bit.ly/2RmKUp2.) Throughout recent history, numerous instances of ARS have been reported, including firefighters responding to the Chernobyl nuclear power plant disaster in 1986.
The clinical presentation of ARS is the result of direct radiation damage to the cells and their components. Exposure to radiation causes a dose-dependent decline in the number of cells by inducing apoptosis and producing free radicals that damage intracellular components. (Hall EJ, Giaccia AJ. Radiobiology for the Radiologist. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2012.)
Ionizing radiation consists of particle waves from radioactive substances (nuclear waste) or electromagnetic waves (x-rays and gamma rays). Ionizing radiation is most commonly emitted by radioactive materials such as uranium, radon, or plutonium. (Merck Manuals Professional Edition. July 2019; https://mrkmnls.co/2FYYERt.) Radiation disrupts all cells, but the effects are most noticeable in short-lived cells such as lymphocytes, hematopoietic precursors cells in the bone marrow, and crypt cells in the intestines.
Absorbed doses of radiation are measured in units called grays (Gy). A roundtrip flight from New York to Los Angeles delivers about 0.05 mGy, annual food and water consumption for the average person is about 0.3 mGy, and a standard chest x-ray is 0.06-0.11 mGy. (United States Nuclear Regulatory Commission. Oct. 2, 2017; http://bit.ly/36Zu3iF.) ARS occurs at much higher exposures, however, starting at 0.7 Gy. (Centers for Disease Control and Prevention. April 4, 2018; http://bit.ly/2RmKUp2.)
Clinically, ARS is characterized by four sequential phases. (Rep Pract Oncol Radiother. 2011;16:123; http://bit.ly/372WPih.) The prodromal phase occurs during the first 48-72 hours post-exposure, and is characterized by headaches, nausea, vomiting, anorexia, tachycardia, and fever. (Centers for Disease Control and Prevention. April 4, 2018; http://bit.ly/2RmKUp2.) The severity of these symptoms depends on the extent of radiation exposure, with doses up to 30 Gy conferring a 100 percent mortality rate in the first 48 hours post-exposure. (Merck Manuals Professional Edition. July 2019; https://mrkmnls.co/2FYYERt.)
Patients with doses below 9 Gy commonly enter a second latent phase characterized by clinical improvement over a period of days. The third phase occurs when the patient begins to manifest his underlying ARS syndrome, categorized into bone marrow, gastrointestinal (GI), and neurological subtypes. This phase may last from hours to months, and mortality is highest in this phase. Recovery is likely if a person survives the third phase, and he then enters the recovery phase.
ARS comprises three different syndromes depending on the cells predominantly affected by the radiation exposure. (Rep Pract Oncol Radiother. 2011;16:138; http://bit.ly/2Nzvble.) (Table 1.) Bone marrow syndrome is characterized by the destruction of bone marrow cells and pancytopenia. This is most commonly seen with radiation doses greater than 0.7 Gy, and typically presents with nausea and vomiting hours to days after the exposure, followed by anorexia, malaise, and fever weeks after the exposure.
Lymphopenia commonly occurs before depression of other cell lines with a 50 percent decline in lymphocyte count in the first 24 hours, which is suggestive of a fatal radiation exposure of 5-10 Gy. Conversely, if the absolute lymphocyte count remains at a level of 50 percent of normal during the first few weeks after exposure, the overall survival rate is close to 90 percent. If death occurs, the primary cause is infection and hemorrhage secondary to neutropenia and thrombocytopenia, respectively.
GI syndrome may present at dose ranges below 1.5 Gy, but survival is dose-dependent with a survival rate of less than one percent for patients exposed to greater than 10 Gy. (Centers for Disease Control and Prevention. April 4, 2018; http://bit.ly/2RmKUp2.) Patients with doses below 1.5 Gy typically present within five days of exposure experiencing nausea, vomiting, and gastric atony. (Gastroenterology. 1988;95:500.) Exposures between 5 and 12 Gy cause extensive mucosal barrier breakdown in the GI tract, leading to severe abdominal pain, diarrhea, malabsorption, nausea, vomiting, and GI bleeding.
The symptoms then recede during the latent phase, which may last up to a week. The manifestation phase, characterized by continued malabsorption and translocation of enteric bacteria through the dysfunctional mucosa, quickly begins. Transposition of bacteria from the gastrointestinal tract and subsequent bacteremia greatly increase mortality in these patients, especially if a concomitant bone marrow syndrome is present. The destruction of GI tract cells results in severe dehydration and electrolyte imbalances, predisposing patients to hemodynamic instability, cardiac arrhythmias, and further end-organ damage.
Cerebrovascular syndrome most commonly occurs when radiation doses exceed 10 Gy. (Rep Pract Oncol Radiother. 2011;16:138; http://bit.ly/2Nzvble.) Progression of illness is accelerated, with symptom onset occurring within minutes of exposure, followed by a shortened latent phase often lasting less than one hour. (Centers for Disease Control and Prevention. April 4, 2018; http://bit.ly/2RmKUp2.)
Impaired capillary circulation, disruption of the blood-brain barrier, and subsequent interstitial edema lead to elevated intracranial pressure and death within three days. (British Institute of Radiology. Oxford: 2001.) The presentation is consistent with increased intracranial pressure, and typically includes ataxia, focal neurological deficits, seizures, papilledema, and possibly a decreased level of consciousness.
A fourth syndrome closely related but generally not considered part of ARS is cutaneous radiation syndrome, which can develop without any of the other ARS symptoms at radiation doses starting at 2 Gy. The syndrome is commonly caused by contaminated clothing and presents with erythema and desquamation, followed by a latent phase where there is intense blistering and ulceration, sometimes resulting in permanent hair loss or necrosis of the exposed skin. (Centers for Disease Control and Prevention. April 4, 2018; http://bit.ly/2RmKUp2.)
ARS is a difficult clinical diagnosis because of its nonspecific symptoms, variable time course, and rarity. Special attention should be given to the history of exposure including occupational history, potential sources like waste containers with unknown contents in remote areas, duration of exposure, use of personal protective equipment, prehospital decontamination, any shielding, distance from exposure, evaluation of symptoms, and time course of the disease.
It is important that the treatment team wears disposable scrubs, hats, masks, and a personal dosimeter to monitor exposure levels. They should also reverse contact precautions to minimize spreading any radioactive material. Make sure that any other life-threatening injuries are treated and that the patient's airway, breathing, and circulation are immediately assessed.
Victims should be treated by standard triage guidelines and with decontamination, which consists of removing all contaminated clothing and washing the patient with soap, which removes as much as 90 percent of radioactive contamination. (Centers for Disease Control and Prevention. April 4, 2018; http://bit.ly/2RmKUp2.) It is important that hospital administrators, including the hospital's radiation officer, be informed and that specific facility policies and protocols for radiation exposure and decontamination are implemented.
Laboratory investigations are helpful to assess lymphocyte depletion and electrolyte derangements. More specifically, serial complete blood counts every two to three hours should be checked to assess lymphocyte depletion for the first eight hours after exposure. Obtain urine and fecal samples when ARS is suspected; these may provide the inpatient team with more information about the level of exposure and the presence of internal contamination. (BMJ. 2004;328:568; http://bit.ly/37azb3K.)
Because the radiation dose may be inferred by using the time between exposure and onset of vomiting, prophylactic doses of antiemetics are not necessary and may obscure the clinical picture. Antiemetics such as ondansetron should be given once the radiation dose is determined by history or onset of emesis. (The Medical Basis for Radiation-Accident Preparedness: The Clinical Care of Victims. Parthenon: Washington, D.C. 2002. p.11.) Hemodynamic resuscitation and supportive care play critical roles in initial emergency management because of the clinical presentation and underlying pathophysiology of ARS, particularly the GI variant. (Nurse Pract. 2003;28:24.)
It is not typical for severe degrees of anemia and thrombocytopenia to occur before two to four weeks following exposure, but requirements vary depending on the patient's condition. Generally, platelets should be maintained at greater than 20,000/L or 75,000/L if surgery is needed. (Rep Pract Oncol Radiother. 2011;16:138; http://bit.ly/2Nzvble.)
Blood products, if needed, should be irradiated to prevent transfusion-associated graft-versus-host disease. Subcutaneous granulocyte-colony stimulating factor (G-CSF) at a dose of 10 mcg/kg daily has been recommended immediately after exposure in individuals receiving whole-body doses of 2 Gy with burns or trauma or in the elderly and patients under 12. (Rep Pract Oncol Radiother. 2011;16:138, http://bit.ly/2Nzvble; J Clin Oncol. 2015;33:3199.)
Serological testing should be done immediately for cytomegalovirus and herpes simplex virus because of increased infection risk from traumatic exposures and neutropenia. Patients positive for either of these should be started on ganciclovir (IV 5 mg/kg/dose every 12 hours for induction) or acyclovir (800 mg orally twice daily). (J Am Osteopath Assoc. 2014;114:702.)
Prophylaxis should also include an antifungal (fluconazole orally 400 mg once daily) to cover opportunistic infections such as Candida until the immune system is reconstituted or the patient is no longer neutropenic. Stable iodine in the form of nonradioactive potassium iodide taken within the first hours of exposure saturates iodine binding sites within the thyroid and prevents incorporation of radioiodine into the gland. (Rep Pract Oncol Radiother. 2011;16:138; http://bit.ly/2Nzvble.) Topical steroids, antibiotics, and antihistamines on ulcers or blisters are the mainstays of treatment for cutaneous syndrome. (J Radiat Res. 2018;59[Suppl 2]:ii54; http://bit.ly/2szg7Nj.)
Disposition is dependent on the METREPOL score from the European Medical Treatment Protocols for Radiation Accident Victims. (Table 2.) Score variables include the delay and severity of symptoms, frequency of vomiting and diarrhea, the presence of abdominal pain and headaches, temperature, loss of consciousness, and laboratory values. (Health Phys. 2010;98:825.) Patients with a score of 1 can be followed as an outpatient, those with a score of 2 or more must be admitted after proper decontamination, and those with a score of 3 or more are unlikely to survive.
We determined that our patient had approximately 2 Gy of radiation exposure. He subsequently had emergent decontamination and received ondansetron and G-CSF because of his age. He was admitted to the intensive care unit and discharged two weeks later.