Topics Topics Acute Radiation Syndrome (ARS) y ( ) • Definition and diagnosis • Treatment Treatment External and Internal Contamination External and Internal Contamination • Definition and diagnosis • Treatment • Treatment Examples Follow Up Care and Research Examples, Follow-Up Care and Research 56
Radiation Injury Radiation Injury • EXPOSURE – Acute Radiation Syndrome (Hematopoietic / Acute Radiation Syndrome (Hematopoietic / GI / CV-CNS / Cutaneous Subsyndromes • EXTERNAL CONTAMINATION • INTERNAL CONTAMINATION INTERNAL CONTAMINATION 57
58 EXPOSURE DUE TO CONTAMINATION Radiation Injury Radiation Injury EXTERNAL EXPOSURE Modified from AFRRI
Radiation Injury Radiation Injury EXPOSURE DUE TO CONTAMINATION EXPOSURE EXTERNAL INTERNAL inhalation Modified from AFRRI 59
Radiation Injury Radiation Injury EXPOSURE DUE TO CONTAMINATION EXPOSURE EXTERNAL INTERNAL ingestion Modified from AFRRI 60
Radiation Injury Radiation Injury EXPOSURE DUE TO CONTAMINATION EXPOSURE EXTERNAL INTERNAL trauma, injection, absorption absorption Modified from AFRRI 61
Medical Effects Medical Effects Acute: Acute: Usually none. ARS possible with large intake or high energy isotopes (e.g. i t k hi h i t ( Polonium) Chronic: Carcinogenesis, chronic radiation injury in target organ, e.g. kidney, lung, bone AFRRI 62
Alexander Litvinenko Alexander Litvinenko Died Nov 2006 Died Nov 2006 from Polonium-210 Photo Source: www.msnbc.msn.com 63
Major Pathways of Release j y Inhalation ( γ , α α , β ) Inhalation ( Cloud Shine ( γ ) Deposition Skin ( β ) Inhalation ( γ , α , β ) Release Ground Inhalation ( Shine ( γ ) Ground from resuspended material from resuspended material Courtesy: F. Harper
Contamination with Cutaneous Radiation Injury Cutaneous Radiation Injury Superficial & partial thickness: Increased permeability Full thickness contamination: Remains in burn eschar Remains in burn eschar AFRRI 65
Major Pathways of Release j y Inhalation ( γ , α , β ) Inhalation ( Cloud Shine ( γ ) Deposition Skin ( β ) Inhalation ( γ , α , β ) Release Ground Inhalation ( Shine ( γ ) Ground from resuspended material from resuspended material Courtesy: F. Harper
Amount of Internal Hazard Amount of Internal Hazard (acts as a poison) • Amount of radionuclide • Radiation characteristics • Target organ T t • Radiation biological half-life AFRRI 67
Possible Contaminating Agents Primary Application that Forms the Radiation Type Primary Form Deposition Basis for Size of Source Nuclide (half-life) Sr-90 Sr 90 Beta (28.6 y) Beta (28 6 y) Ceramic (SrTiO 3 ) Ceramic (SrTiO 3 ) Large radioisotopic thermal Large radioisotopic thermal Bone Bone generator (RTG) Cs-137 Beta + Ba-137m Salt (CsCl) Irradiator Whole body Gamma (30.17 y) I-131 Beta, Gamma Salt Fission product, nuclear weapons Thyroid (8.02 d) testing, nuclear medicine H-3 Beta (12.3 y) Gas/liquid Gun sights, nuclear warheads Kidney Alpha (4.5x10 12 y) U-238 Metal Depleted munitions Kidney Lung (inhaled) Pu-238 Alpha (87.75 y) Ceramic (PuO 2 ) RTG used for the Cassini Saturn space probe Bone Am-241 Alpha (432.2 y) Pressed ceramic Single well-logging source Liver powder (AmO 2 ) Bone Bone Bone Ra 226 Ra-226 Alpha (1600 y) Alpha (1600 y) Salt Salt Old medical therapy sources Old medical therapy sources (RaSO 4 ) 68
69 Large Large source scenarios Medium Medium Large Large Modified from AFRRI
Biological Half-Life Biological Half Life Definition: Definition: The time for half the atoms of a substance to be removed from the body. Examples: – Cesium ( 137 Cs): 12 – 165 days (shortest in infants) ( ) y ( ) – Tritium ( 3 H): 10 - 12 days – Plutonium (Pu): bone = 100 yrs, liver = 40 yrs – Uranium (U): bone = 300 days, kidney = 15 days Uranium (U): bone = 300 days kidney = 15 days lung = 120-1470 days (size/solubility) NCRP 65, pp 78, 108, 90, 111, 1980. 70
Inhalation Pathway Inhalation Pathway • Most efficient route • Inhale radiation-emitting particulate matter (we • Inhale radiation-emitting particulate matter (we do not “inhale radiation”) • Particle size — key factor (0 1 – 5 microns) Particle size key factor (0.1 5 microns) • Secondary source for ingestion • Solubility — important • Solubility — important AFRRI 71
Clearance Times from the Clearance Times from the Respiratory Tract Structure Clearance Time Trachea 6 min Bronchi 1 hr Bronchioles 4 hr Terminal Bronchioles 10 hr Al Alveoli li 100 100 - 1500+ days 1500 d NCRP 65, p. 23, 1980. 72
Topics Topics Acute Radiation Syndrome (ARS) y ( ) • Definition and diagnosis • Treatment Treatment External and Internal Contamination External and Internal Contamination • Definition and diagnosis • Treatment • Treatment Examples Follow Up Care and Research Examples, Follow-Up Care and Research 73
Initial Patient Management Initial Patient Management • First address life-threatening Fi t dd lif th t i conditions / injuries — the ABC’s • Initial survey (frisk with RADIACs) • Nasal swabs-do early N l b d l Health care workers have never been hurt caring for contaminated patients AFRRI 74
First Steps: External Decontamination 1. Remove patient’s clothing. 2. Wash patient with mild soap and water (or take a shower). ( ) 95+% EFFECTIVE AFRRI 75
General Management to Reduce Internal Dose (Consider as a Poison) a. Reduce intake, uptake, deposition b. Increase excretion b. Increase excretion c. Decide “Risk versus Benefit” for treatment AFRRI 76
Classes of Some Drugs for Treatment of Internal Contamination • Blocking agents, e.g. potassium iodide Bl ki t t i i did • Chelating agents, e.g. DTPA • Diluting agents, e.g. water • Ion exchange resins e g Prussian Blue Ion exchange resins, e.g. Prussian Blue NCRP Report 65, 1980, Section 7 77
Potassium Iodide (KI) for R di Radioactive Iodine (RAI) Protection ti I di (RAI) P t ti • Indication : Protection against RAI to reduce risk of thyroid cancer • Contraindication : Iodine hypersensitivity • Availability : over the counter Availability : over the counter • Possible side effects: — Allergic reaction, GI upset, thyrotoxicosis — Hypothyroidism in neonates: Get TSH • Use : — Administer NLT 4 hours after exposure to RAI — Administer NLT 4 hours after exposure to RAI — Prioritize sheltering for pregnant and lactating females and those allergic to KI FDA Guidance 2001. 78
Threshold Thyroid Radioactive Exposures and Recommended Doses Exposures and Recommended Doses of Potassium Iodide (KI) Predicted P di t d KI dose KI d Thyroid Exposure daily mg Adults > 40 yrs Adults > 40 yrs > 500 cGy (5 Gy) > 500 cGy (5 Gy) 130 130 Adults 18-40 yrs > 10 cGy 130 Pregnant / lactating > 5 cGy 130 females Age 3 -18 yrs Age 3 18 yrs > 5 cGy > 5 cGy 65 (130 if large) 65 (130 if large) 1 month – 3 yrs > 5 cGy 32 Birth – 1 month > 5 cGy 16 FDA Guidance 2001. 79
80 Potassium Iodide (KI) Potassium Iodide (KI) 130 mg/tablet 1000 mg/ml 65 mg/ml AFRRI
Chelating Agents: e.g. DTPA Chelating Agents: e.g. DTPA Diethylenetriaminepentaacetate (Trisodium Calcium / Zinc Salts) ( ) • FDA approved, 2004 – For plutonium (Pu) For plutonium (Pu), americium (Am), curium (Cu) – Available in Strategic National Stockpile (SNS) National Stockpile (SNS) – Prescription, injection • May remove 60-90% of y soluble plutonium – When started early AFRRI 81
Other Chelating Agents Other Chelating Agents • Defarasirox (FDA 2005 oral for Fe* ) • Defarasirox (FDA 2005, oral for Fe ) • Deferoxamine ( Fe* , Pu) • Dimercaprol ( As*, Au*, Hg* , Cr Ni, Pb) , , g , p ( , ) • EDTA ( Pb* , other metals) • Penicillamine ( Cu* , Au, Hg, Pb) • Sevelamer ( P* ) • Succimer ( Pb* ) * FDA approved for these indications only 82
Ion Exchange Resins: e g Prussian Blue e.g. Prussian Blue (ferric ferrocyanide) • FDA approved, 2003 – Prescription drug available in Strategic National Stockpile Strategic National Stockpile • Indicated for Cesium and Thallium • Dosage – Oral, adults 3 grams tid (18 capsules) per day; ages 2-12, 1 gram tid (6 capsules) per day, possibly for weeks • Side Effect: Possible constipation • Reduces 137 Cs biological Reduces Cs biological half-time to <30% previous value AFRRI 83
DILEMMAS DILEMMAS • Rapid diagnosis – Where to send specimens? Where to send specimens? – Location and use of whole body counters? • When to treat? • When to treat? 5-10 x Annual Limit? 5-10 x Annual Limit? • When to stop treatment? • Special populations, e.g. children, pregnant females, elderly 84
Remember FDA Indications ? Remember FDA Indications ? Drug Drug Indication Indication Availability Availability DTPA Potassium Iodide (KI) Prussian Blue 85
Remember FDA Indications ? Remember FDA Indications ? Drug Drug Indication Indication Availability Availability DTPA Plutonium Rx A Americium i i SNS* Curium Potassium P t i R di i did Radioiodides OTC OTC Iodide (KI) SNS Prussian Blue Cesium Rx Thallium SNS * SNS is the Strategic National Stockpile 86
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