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	More about Acute Radiation Syndrome (ARS) Time Phases of ARS Prodromal Syndrome of ARS Importance and Methods of Estimating Whole-Body Dose Biodosimetry Dose Reconstruction See also: Manage Subsyndromes of Acute Radiation Syndrome See also: Time/Dose Effects in Acute Radiation Syndrome Time Phases of ARS1,2 Introduction Prodromal stage Classic symptoms depend on dose: Nausea Vomiting Anorexia Diarrhea Symptoms occur from minutes to days following exposure. Symptoms may last (episodically) for minutes up to several days. Latent stage Patient looks and feels generally healthy for a few hours or even up to a few weeks. Manifest illness stage Symptoms depend on the specific syndrome (see table below and table of subsyndromes). Symptoms last from hours up to several months. Recovery or death stage Patients who do not recover will die within days to months of exposure Recovery process lasts from several weeks up to 2 years. Table 1: Time Phases of Acute Radiation Syndromes2 View/Print as PDF (PDF - 74 KB) Syndrome Dose (Gray)* Prodromal Latent Manifest Illness Recovery or Death Hematopoietic (Bone Marrow) Onset Onset as low as 0.3 Gy in compromised hosts Typical onset 1 Gy, rarely acutely clinically significant below this level unless complicated by injury or other host factors Symptoms Anorexia Nausea Vomiting Onset 1 hour to 2 days after exposure Duration Minutes to days Bone marrow Marrow stem cells dying, although patient may appear and feel well Duration 1 to 6 weeks Symptoms Anorexia, Fever, and Malaise Signs Drop in all blood cell counts occurs for weeks Causes of death Infection Hemorrhage Survival decreases with increasing dose. Time to death Weeks to months Bone marrow Bone marrow regrows in most cases Time to recovery Weeks to 2 yrs after exposure Reflects dose & complications, +/- transplant done/success Causes of death Death may occur in some individuals at doses as low as 1.2 Gy with Adverse host factors ARS/BMT complications The LD50/60† About 2.5 - 5 Gy Gastrointestinal (GI) Onset Onset as low as 6 Gy May occur at lower dose if Whole body dose high Dose rate rapid Host GI tract compromised At doses >12 Gy, GI mortality rate exceeds hematologic mortality rate Symptoms Anorexia Severe nausea Vomiting Cramps Diarrhea Onset Hours after exposure Duration At least 2 days Dose dependent GI cells Marrow stem cells and cells lining GI tract are dying, although patient may appear and feel well. Duration < 1 week Symptoms Malaise Anorexia Severe diarrhea Fever Dehydration Electrolyte imbalance Causes of death Infection Dehydration Electrolyte imbalance Time to death Days to weeks, depending on dose LD100‡ is about 10 Gy Neurovascular Onset Typical onset about 20 to 30 Gy Onset with lower dose if complicated by other host factors Symptoms Extreme nervousness and confusion Severe nausea, vomiting, and watery diarrhea Loss of consciousness Burning sensations of the skin Onset Within minutes of exposure Duration Lasts for minutes to hours Symptoms Patient may return to partial functionality Duration Stage may last for hours but often is less Death Within 3 days of exposure Symptoms Return of watery diarrhea, convulsions, and coma Onset Occurs 5 to 6 hours after exposure Death Occurs within 3 days of exposure No recovery expected * The absorbed doses quoted are “gamma equivalent” values. Neutrons or protons generally produce the same effects as gamma rays, beta particles, 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: dose necessary to kill 50% of the exposed population in 60 days. ‡ The LD100: dose necessary to kill 100% of the exposed population. top of page Prodromal Syndrome of ARS4 What is the prodromal syndrome (the prodromal phase of the Acute Radiation Syndrome)? Acute symptoms resulting from acute whole-body exposure. The prodromal phase of ARS usually occurs in the first 48 hours but may develop up to 6 days after exposure. Prodromal symptoms are usually considered to be anorexia, apathy, nausea, vomiting, diarrhea, fever, loss of consciousness, tachycardia, headache. What do you learn by evaluating a victim's prodromal syndrome? A victim's prodromal syndrome characteristics predict clinical outcome, and this information can be used for triage and clinical treatment planning. (Note: Prodromal syndrome characteristics can be modified by concomitant injury.) Rapid and severe prodromal syndrome usually predicts a poor clinical outcome that may be complicated by severe forms of the gastrointestinal and hematopoietic subsyndromes of the ARS and, at worst, the neurovascular subsyndrome. If less than 1 Gray of exposure, the prodromal syndrome is usually mild or absent or less was received. If patients' symptoms begin > 2 hours after exposure, they were probably exposed to doses <2 Gy. If symptoms occur < 2 hours, that usually indicates significant and potentially lethal whole-body exposures exceeding 2 Gy. At doses between 2 and 10 Gy, it is difficult to establish a prognosis based solely on the existence and/or severity of the prodromal syndrome. At high doses between 10 and 20 Gy, prodromal symptoms occur in virtually all patients within minutes of exposure. These gradually merge into loss of consciousness and hypotension which are components of the neurovascular subsyndrome of ARS. Death often occurs within a few days to weeks after this level of exposure. The neurovascular subsyndrome can present in mild form at doses as low as 7.5 Gy but typically will not be severe until doses of 10 Gy have been received. Almost all patients who present with severe neurovascular subsyndrome will die. Those with severe neurovascular subsyndrome who live long enough will also develop a severe form of the gastrointestinal and hematopoietic subsyndromes of ARS before death. top of page Importance and Methods of Estimating Whole-Body Dose1-5 Why is it important to calculate a radiation victim's whole-body dose? ARS severity depends on Whole-body exposure dose Radiation dose rate Host factors, e.g., infants, children, elderly, diminished immune function, and whether or not injury complicates ARS. The higher the exposure dose, generally... The earlier the clinical onset after the event The more severe the clinical manifestations The worse the clinical outcome Knowing correct whole-body dose information will facilitate Selection of appropriate prophylactic and therapeutic measures Determination of prognosis, which is especially useful in mass casualty situations when resources may be limited Transfer of patient to a facility with the expertise to handle the complex problems associated with severe ARS. How can you estimate whole-body dose from clinical factors (biodosimetry)? See interactive tool. Are there other ways to reconstruct a patient's exposure dose without clinical biodosimetry? Use key factors in taking a history: time, distance, shielding (see Figure) Time the patient spent in the radiation field Location of the patient in relation to the epicenter of the radiation event Presence or absence of any significant shielding material that could have attenuated the dose Use clinical factors related to ARS subsyndromes5 Evaluate subsyndrome severity score for the 4 ARS Subsyndromes Higher severity score of any subsyndrome is generally correlated with higher exposure dose Subsyndromes (a.k.a. Cerebrovascular) Evaluate patient manifestations with respect to the four time phases of ARS subsyndromes: Generally, the shorter time to onset of any subsyndrome correlated with higher dose exposure ARS Phases Prodromal Latent Manifest illness Recovery or death Obtain from incident radiation experts any information about the geographic location of the radiation dose plume and attempt to estimate patient's location in the target area Was patient wearing a personal radiation dosimeter? Were there stationary geographic dosimeters in place near the patient's location that provide dose information relevant to estimating the patient's dose? What do you do if the estimates of whole-body dose are conflicting? Use the highest estimate top of page References Waselenko JK, MacVittie TJ, Blakely WF, Pesik N, Wiley AL, Dickerson WE, Tsu H, Confer DL, Coleman CN, Seed T, Lowry P, Armitage JO, Dainiak N; Strategic National Stockpile Radiation Working Group. Medical management of the acute radiation syndrome: recommendations of the Strategic National Stockpile Radiation Working Group. Ann Intern Med. 2004 Jun 15;140(12):1037-51. [PubMed Citation] Acute Radiation Syndrome: A Fact Sheet for Physicians (HHS/CDC) Waselenko JK, Armitage JO, Dainiak N. Treatment of radiation injury in the adult. www.UpToDate.com (Subscription required) Waselenko JK, Dainiak N. Biology and clinical features of radiation injury in adults. www.UpToDate.com (Subscription required) Fliedner TM, Friesecke I, Beyrer K. Medical Management of Radiation Accidents: Manual on the Acute Radiation Syndrome. Oxford: British Institute of Radiology, 2001.

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