acute radiation syy()ndrome (ars) · acute radiation syndrome (ars)acute radiation syndrome (ars)...
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TopicsTopicsAcute Radiation Syndrome (ARS)y ( )• Definition and diagnosis• TreatmentTreatment
External and Internal ContaminationExternal and Internal Contamination• Definition and diagnosis• Treatment• Treatment
Examples Follow Up Care and ResearchExamples, Follow-Up Care and Research
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Radiation InjuryRadiation Injury
• EXPOSURE– Acute Radiation Syndrome (Hematopoietic /Acute Radiation Syndrome (Hematopoietic /
GI / CV-CNS / Cutaneous Subsyndromes
• EXTERNAL CONTAMINATIONINTERNAL CONTAMINATION• INTERNAL CONTAMINATION
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Radiation InjuryRadiation InjuryEXPOSURE
EXPOSURE DUE TO CONTAMINATION
EXTERNAL
58Modified from AFRRI
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Radiation InjuryRadiation InjuryEXPOSURE
EXPOSURE DUE TO CONTAMINATION
inhalation
EXTERNAL INTERNAL
59Modified from AFRRI
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Radiation InjuryRadiation InjuryEXPOSURE
EXPOSURE DUE TO CONTAMINATION
ingestion
EXTERNAL INTERNAL
60Modified from AFRRI
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Radiation InjuryRadiation InjuryEXPOSURE
EXPOSURE DUE TO CONTAMINATION
EXTERNAL INTERNAL
trauma, injection, absorptionabsorption
61Modified from AFRRI
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Medical EffectsMedical Effects
Acute:Acute:Usually none. ARS possible with large i t k hi h i t (intake or high energy isotopes (e.g. Polonium)
Chronic:Carcinogenesis, chronic radiation injury in target organ, e.g. kidney, lung, bone
62AFRRI
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Alexander LitvinenkoAlexander Litvinenko
Died Nov 2006Died Nov 2006 from Polonium-210
63Photo Source: www.msnbc.msn.com
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Major Pathways of Releasej y
CloudInhalation (Inhalation (γγ,,αα,,ββ))
Shine (γ)Deposition
Skin (β)
Release GroundShine (γ)
Inhalation (Inhalation (γγ,,αα,,ββ))from resuspended materialfrom resuspended materialGround
Courtesy: F. Harper
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Contamination withCutaneous Radiation InjuryCutaneous Radiation Injury
Superficial & partial thickness:Increased permeability
Full thickness contamination:Remains in burn escharRemains in burn eschar
65AFRRI
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Major Pathways of Releasej y
CloudInhalation (Inhalation (γγ,,αα,,ββ))
Shine (γ)Deposition
Skin (β)
Release GroundShine (γ)
Inhalation (Inhalation (γγ,,αα,,ββ))from resuspended materialfrom resuspended materialGround
Courtesy: F. Harper
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Amount of Internal HazardAmount of Internal Hazard (acts as a poison)
• Amount of radionuclide• Radiation characteristics
T t• Target organ• Radiation biological half-life
67AFRRI
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Possible Contaminating Agents
Nuclide
Primary Radiation Type
(half-life)Primary Form Application that Forms the
Basis for Size of Source Deposition
Sr-90 Beta (28 6 y) Ceramic (SrTiO3) Large radioisotopic thermal BoneSr 90 Beta (28.6 y) Ceramic (SrTiO3) Large radioisotopic thermal generator (RTG)
Bone
Cs-137 Beta + Ba-137m Gamma (30.17 y)
Salt (CsCl) Irradiator Whole body
I-131 Beta, Gamma (8.02 d)
Salt Fission product, nuclear weapons testing, nuclear medicine
Thyroid
H-3 Beta (12.3 y) Gas/liquid Gun sights, nuclear warheads Kidney
U-238 Alpha (4.5x1012 y) Metal Depleted munitions Kidney
Pu-238 Alpha (87.75 y) Ceramic (PuO2) RTG used for the Cassini Saturn Lung (inhaled)space probe Bone
Am-241 Alpha (432.2 y) Pressed ceramic powder (AmO2)
Single well-logging source LiverBone
Ra 226 Alpha (1600 y) Salt Old medical therapy sources BoneRa-226 Alpha (1600 y) Salt(RaSO4)
Old medical therapy sources Bone
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Large source scenarios
Large
Large
MediumMedium
Large
69Modified from AFRRI
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Biological Half-LifeBiological Half LifeDefinition:Definition:
The time for half the atoms of a substance to be removed from the body.
Examples:– Cesium (137Cs): 12 – 165 days (shortest in infants)( ) y ( )– Tritium (3H): 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 dayslung = 120-1470 days (size/solubility)
NCRP 65, pp 78, 108, 90, 111, 1980. 70
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Inhalation PathwayInhalation 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
71AFRRI
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Clearance Times from theClearance Times from the Respiratory Tract
Structure Clearance Time
Trachea 6 minBronchi 1 hrBronchioles 4 hrTerminal Bronchioles 10 hrAl li 100 1500 dAlveoli 100 - 1500+ days
NCRP 65, p. 23, 1980. 72
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TopicsTopicsAcute Radiation Syndrome (ARS)y ( )• Definition and diagnosis• TreatmentTreatment
External and Internal ContaminationExternal and Internal Contamination• Definition and diagnosis• Treatment• Treatment
Examples Follow Up Care and ResearchExamples, Follow-Up Care and Research
73
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Initial Patient ManagementInitial Patient Management
Fi t dd lif th t i• First address life-threatening conditions / injuries — the ABC’s
• Initial survey (frisk with RADIACs)N l b d l• Nasal swabs-do early
Health care workers have never been hurt caring for contaminated patients
74AFRRI
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First Steps:
External Decontamination
1. Remove patient’s clothing.
2. Wash patient with mild soap and
( )water (or take a shower).
95+%EFFECTIVE
75AFRRI
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General Management toReduce Internal Dose
(Consider as a Poison)
a. Reduce intake, uptake, depositionb. Increase excretionb. Increase excretionc. Decide “Risk versus Benefit” for treatment
76AFRRI
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Classes of Some Drugs for Treatment of Internal
Contamination
Bl ki t t i i did• Blocking agents, e.g. potassium iodide• Chelating agents, e.g. DTPA• Diluting agents, e.g. water• Ion exchange resins e g Prussian BlueIon exchange resins, e.g. Prussian Blue
77NCRP Report 65, 1980, Section 7
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Potassium Iodide (KI) forR di ti I di (RAI) P t tiRadioactive Iodine (RAI) Protection
• Indication: Protection against RAI to reduce risk ofthyroid cancer
• Contraindication: Iodine hypersensitivity• Availability: over the counterAvailability: 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
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Threshold Thyroid Radioactive Exposures and Recommended DosesExposures and Recommended Doses
of Potassium Iodide (KI)P di t d KI dPredicted
Thyroid ExposureKI dose daily mg
Adults > 40 yrs > 500 cGy (5 Gy) 130Adults > 40 yrs > 500 cGy (5 Gy) 130
Adults 18-40 yrs > 10 cGy 130
Pregnant / lactating females
> 5 cGy 130
Age 3 -18 yrs > 5 cGy 65 (130 if large)Age 3 18 yrs > 5 cGy 65 (130 if large)
1 month – 3 yrs > 5 cGy 32
Birth – 1 month > 5 cGy 16
FDA Guidance 2001. 79
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Potassium Iodide (KI)Potassium Iodide (KI)
130 mg/tablet
65 mg/ml 1000 mg/ml
80AFRRI
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Chelating Agents: e.g. DTPAChelating Agents: e.g. DTPADiethylenetriaminepentaacetate(Trisodium Calcium / Zinc Salts)
• FDA approved, 2004– For plutonium (Pu)
( )
For plutonium (Pu), americium (Am), curium (Cu)
– Available in StrategicNational Stockpile (SNS)National Stockpile (SNS)
– Prescription, injection
• May remove 60-90% of ysoluble plutonium– When started early
81AFRRI
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Other Chelating AgentsOther Chelating Agents
• Defarasirox (FDA 2005 oral for Fe*)• Defarasirox (FDA 2005, oral for Fe )• Deferoxamine (Fe*, Pu)• Dimercaprol (As*, Au*, Hg*, Cr Ni, Pb)p ( , , g , , )• EDTA (Pb*, other metals)• Penicillamine (Cu*, Au, Hg, Pb)• Sevelamer (P*)• Succimer (Pb*)* FDA approved for these indications only
82
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Ion Exchange Resins: e g Prussian Bluee.g. Prussian Blue
(ferric ferrocyanide)• FDA approved, 2003
– Prescription drug available in Strategic National StockpileStrategic 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 137Cs biologicalReduces Cs biological
half-time to <30% previous value
83AFRRI
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DILEMMASDILEMMAS
• Rapid diagnosis– Where to send specimens?Where to send specimens?– Location and use of whole body counters?
• When to treat? 5-10 x Annual Limit?• When to treat? 5-10 x Annual Limit? • When to stop treatment?• Special populations, e.g. children,
pregnant females, elderly
84
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Remember FDA Indications ?Drug Indication Availability
Remember FDA Indications ?Drug Indication Availability
DTPA
Potassium Iodide (KI)Prussian Blue
85
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Remember FDA Indications ?Drug Indication Availability
Remember FDA Indications ?Drug Indication Availability
DTPA Plutonium A i i
RxAmericium
CuriumSNS*
P t i R di i did OTCPotassium Iodide (KI)
Radioiodides OTCSNS
Prussian Blue CesiumThallium
RxSNS
* SNS is the Strategic National Stockpile86
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Treatment of?Fission Products ?
• No specific drug since there may be dozens of isotopes present
• Prevent inhalation and ingestion• Shelter in placep• External decontamination• Consider irrigation cathartics andConsider irrigation, cathartics and
laxatives
87AFRRI
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TopicsTopics
Acute Radiation Syndrome (ARS)Acute Radiation Syndrome (ARS)• Definition and diagnosis• TreatmentTreatment
External and Internal Contamination• Definition and diagnosis• Treatment
Examples, Follow-Up Care, Research Areas
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E l f M di l RExamples of Medical Responseto Radiation Accidents
• 1986 Chernobyl, Ukraine (former USSR)• 1987 Goiânia, Brazil• 1999 Tokaimura, Japan
89
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CHERNOBYLApril 1986
Worst Radiation Accidentin Historyin History
Photo: Monitoring ChernobylPhoto: Monitoring ChernobylReactor from Helicopter
Adapted from AFRRI 90
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Chernobyl M di l RMedical Response
• 500 personnel hospitalized– > 100 personnel received > 1 Grayp y
• Intensive Supportive Care– Clean environment / isolation– Prophylactic and therapeutic antimicrobials– Transfused RBC and platelets– “High rate of survival up to 6 Gray”– High rate of survival up to 6 Gray
Gale, R.P., “Lessons from Chernobyl”, JAMA, Aug 1987. 91
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Chernobyl:
13 transplants for victims with doses 5 6 13 Gy
Bone Marrow Transplants• 13 transplants for victims with doses 5.6 – 13 Gy• 2 survivors (as of 1989 after doses of 8.7 & 5.6 Gy)• Causes of DeathCauses of Death
– Burns 5– Interstitial pneumonitis 3– Graft versus Host Disease 2– Renal failure & ARDS 1
11 deaths11 deaths
• Conclusion: No clear evidence that bone marrow transplants were beneficialtransplants were beneficial
Gale et al, NEJM, 1989; 321: 205-212 / UNSCEAR 2000 Appendix J. 92
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Chernobyl at 20+ YearsChernobyl at 20+ Years
• About 50 deaths due to radiation injury• About 50 deaths due to radiation injury• 4000+ childhood thyroid cancer• Long term psycho social impact• Long-term psycho-social impact
– Evacuation of 135,000– Victim mentalityVictim mentality– Expecting medical problems– Socio-economic problemsp
93Chernobyl Forum, 2005.
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Goiânia, Brazil, September 1987
“ Worst radiation accident inin
the Western Hemisphere”p
Science, 1987Source: Science, 1987~ 2.5 cm diameter~ 1400 Ci, Cesium-137as CsCl salt (powder)as CsCl salt (powder)
94Adapted from AFRRI
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Goiânia Cesium-137 Incident: Di t b b i ?Dirty bomb scenario ?
• 130,000 people (10%) came to ER /temporary screening locations
• 250 (0.2%) were t i t dcontaminated
• 20 (0.01%) required t t ttreatment
95
IAEA Pub “The Radiological Accident in Goiania”, 1988available at www-pub.iaea.org
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Goiânia Cesium-137 Incident: D /Th I f ti
• 20 patients ARS dose exposure: 1 - 7 1 Gy
Dose/Therapy Information• 20 patients, ARS dose exposure: 1 - 7.1 Gy• Internal contamination: + urine
+ stool+ perspiration+ perspiration
• TreatmentChelation therapy: Prussian BluepyInfection/sepsis: antibiotics, antifungal, antiviral Bone marrow stimulation: GM-CSF
• Outcome: 4 deaths (4-6 Gy)
96
IAEA Pub “The Radiological Accident in Goiania”, 1988available at www-pub.iaea.org
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Tokaimura, Japan 1999Incident: Criticality accident
B B
A
A
97Endo & Yamaguchi, Radiat Res 159, 2003.
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Tokaimura, Japan:P ti t APatient A
• Patient A holding funnel• Estimated dose 16-25 Gy-Equivalent
f• Rapid loss of consciousness• Suffered from cutaneous radiation burns, and
intestinal renal and respiratory impairmentintestinal, renal and respiratory impairment• Numerous problems with vascular
hyperpermeabilityhyperpermeability
98Adapted from AFRRI
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Patient A InterventionsPatient A Interventions
• Cytokines (G-CSF)• Peripheral stem cell transfusion from HLA-identical
sibling• Digestive tract decontamination• Crypt cell stimulation with L-glutamine• High dose pentoxyphylline to control vascular injury • Expired 84 days after exposure from cardiac event
99Adapted from AFRRI
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Tokaimura, Japan:P ti t BPatient B
• Patient B pouring uranium• Estimated dose 6-10 Gy-Equivalent • GI tract decontamination• Crypt cell stimulation with L-glutamine• G-CSF cytokine bone marrow stimulation• Cord blood cell transfusion• Vascular injury control with high-dose
pentoxiphylline
100Adapted from AFRRI
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Patient B Interventions (contd)Patient B Interventions (contd)
• Severe cutaneous burns required multiple skin grafts
• Developed radiation pneumonitis and pulmonary hemorrhagepulmonary hemorrhage
• Expired 7 months after incident in April 2000Expired 7 months after incident in April 2000
101Adapted from AFRRI
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Long Term and Follow-Up CareLong Term and Follow Up Care
• Multiple Organ Dysfunction: pulmonary, p g y p yhepatic, renal and cardiac failure
• Possible late effectsPossible late effects– Malignancies: Leukemia early, then breast,
intestinal, lung, thyroid etc., g, y– Cataracts, sterility– In-utero and childhood effectsIn utero and childhood effects– Psychosocial
• Need long term screening• Need long term screening
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Research AreasResearch Areas
• Biodosimetry• Biodosimetry– Genomic and proteomic predictors of dose
Hi h th h t– High through-put screens• Radiation mitigators and protectants
– Amifostine - no– Improved chelating agents– Captopril, statins, vitamins, etc.
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Summary of Topics Covered:Acute Radiation Syndrome (ARS)• Definition and diagnosis• Definition and diagnosis• Treatment
External and Internal ContaminationD fi i i d di i• Definition and diagnosis
• Treatment
Examples, Follow-Up Care, Research Areas
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Questions?