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
56
Radiation InjuryRadiation Injury
• EXPOSURE– Acute Radiation Syndrome (Hematopoietic /Acute Radiation Syndrome (Hematopoietic /
GI / CV-CNS / Cutaneous Subsyndromes
• EXTERNAL CONTAMINATIONINTERNAL CONTAMINATION• INTERNAL CONTAMINATION
57
Radiation InjuryRadiation InjuryEXPOSURE
EXPOSURE DUE TO CONTAMINATION
EXTERNAL
58Modified from AFRRI
Radiation InjuryRadiation InjuryEXPOSURE
EXPOSURE DUE TO CONTAMINATION
inhalation
EXTERNAL INTERNAL
59Modified from AFRRI
Radiation InjuryRadiation InjuryEXPOSURE
EXPOSURE DUE TO CONTAMINATION
ingestion
EXTERNAL INTERNAL
60Modified from AFRRI
Radiation InjuryRadiation InjuryEXPOSURE
EXPOSURE DUE TO CONTAMINATION
EXTERNAL INTERNAL
trauma, injection, absorptionabsorption
61Modified from AFRRI
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
Alexander LitvinenkoAlexander Litvinenko
Died Nov 2006Died Nov 2006 from Polonium-210
63Photo Source: www.msnbc.msn.com
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
Contamination withCutaneous Radiation InjuryCutaneous Radiation Injury
Superficial & partial thickness:Increased permeability
Full thickness contamination:Remains in burn escharRemains in burn eschar
65AFRRI
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
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
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
68
Large source scenarios
Large
Large
MediumMedium
Large
69Modified from AFRRI
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
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
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
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
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
First Steps:
External Decontamination
1. Remove patient’s clothing.
2. Wash patient with mild soap and
( )water (or take a shower).
95+%EFFECTIVE
75AFRRI
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
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
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
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
Potassium Iodide (KI)Potassium Iodide (KI)
130 mg/tablet
65 mg/ml 1000 mg/ml
80AFRRI
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
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
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
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
Remember FDA Indications ?Drug Indication Availability
Remember FDA Indications ?Drug Indication Availability
DTPA
Potassium Iodide (KI)Prussian Blue
85
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
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
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
E l f M di l RExamples of Medical Responseto Radiation Accidents
• 1986 Chernobyl, Ukraine (former USSR)• 1987 Goiânia, Brazil• 1999 Tokaimura, Japan
89
CHERNOBYLApril 1986
Worst Radiation Accidentin Historyin History
Photo: Monitoring ChernobylPhoto: Monitoring ChernobylReactor from Helicopter
Adapted from AFRRI 90
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
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
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.
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
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
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
Tokaimura, Japan 1999Incident: Criticality accident
B B
A
A
97Endo & Yamaguchi, Radiat Res 159, 2003.
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
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
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
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
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
102
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.
103
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
104
Questions?