Topics Topics Acute Radiation Syndrome (ARS) y ( ) Definition - - PowerPoint PPT Presentation

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

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Radiation Injury Radiation Injury

• EXPOSURE

– Acute Radiation Syndrome (Hematopoietic / Acute Radiation Syndrome (Hematopoietic / GI / CV-CNS / Cutaneous Subsyndromes

• EXTERNAL CONTAMINATION

INTERNAL CONTAMINATION

• INTERNAL CONTAMINATION

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Radiation Injury Radiation Injury

EXPOSURE EXPOSURE DUE TO CONTAMINATION EXTERNAL

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Modified from AFRRI

Radiation Injury Radiation Injury

EXPOSURE EXPOSURE DUE TO CONTAMINATION

inhalation

EXTERNAL INTERNAL

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Modified from AFRRI

Radiation Injury Radiation Injury

EXPOSURE EXPOSURE DUE TO CONTAMINATION

ingestion

EXTERNAL INTERNAL

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Modified from AFRRI

Radiation Injury Radiation Injury

EXPOSURE EXPOSURE DUE TO CONTAMINATION EXTERNAL INTERNAL

trauma, injection, absorption absorption

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Modified from AFRRI

Medical Effects Medical 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

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AFRRI

Alexander Litvinenko Alexander Litvinenko Died Nov 2006 Died Nov 2006 from Polonium-210

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Photo Source: www.msnbc.msn.com

Major Pathways of Release j y

Cloud Inhalation ( Inhalation (γ,α α,β) Shine (γ) Deposition

Skin (β)

Release Ground Shine (γ) Inhalation ( Inhalation (γ,α,β) from resuspended material from resuspended material Ground

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

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AFRRI

Major Pathways of Release j y

Cloud Inhalation ( Inhalation (γ,α,β) Shine (γ) Deposition Skin (β) Release Ground Shine (γ) Inhalation ( Inhalation (γ,α,β) from resuspended material from resuspended material Ground

Courtesy: F. Harper

Amount of Internal Hazard Amount of Internal Hazard (acts as a poison)

• Amount of radionuclide
• Radiation characteristics

T t

• Target organ
• Radiation biological half-life

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AFRRI

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 Bone Sr 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 Liver Bone Ra 226 Alpha (1600 y) Salt Old medical therapy sources Bone Ra-226 Alpha (1600 y) Salt (RaSO4) Old medical therapy sources Bone

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Large source scenarios

Large Large Medium Medium Large

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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 (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 days lung = 120-1470 days (size/solubility)

NCRP 65, pp 78, 108, 90, 111, 1980.

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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

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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 li 100 1500 d Alveoli 100 - 1500+ days

NCRP 65, p. 23, 1980.

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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

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Initial Patient Management Initial 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

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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

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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

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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 Blue

Ion exchange resins, e.g. Prussian Blue

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NCRP Report 65, 1980, Section 7

Potassium Iodide (KI) for R di ti I di (RAI) P t ti Radioactive Iodine (RAI) Protection

• 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.

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Threshold Thyroid Radioactive Exposures and Recommended Doses Exposures and Recommended Doses

• f Potassium Iodide (KI)

P di t d KI d Predicted Thyroid Exposure KI dose daily mg Adults > 40 yrs > 500 cGy (5 Gy) 130 Adults > 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.

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Potassium Iodide (KI) Potassium Iodide (KI)

130 mg/tablet 65 mg/ml 1000 mg/ml

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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

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AFRRI

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)

p ( , , g , , )

• EDTA (Pb*, other metals)
• Penicillamine (Cu*, Au, Hg, Pb)
• Sevelamer (P*)
• Succimer (Pb*)

* FDA approved for these indications only

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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 137Cs biological

Reduces Cs biological half-time to <30% previous value

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AFRRI

DILEMMAS DILEMMAS

• 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

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Remember FDA Indications ?

Drug Indication Availability

Remember FDA Indications ?

Drug Indication Availability DTPA Potassium Iodide (KI) Prussian Blue

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Remember FDA Indications ?

Drug Indication Availability

Remember FDA Indications ?

Drug Indication Availability DTPA Plutonium A i i Rx Americium Curium SNS* P t i R di i did OTC Potassium Iodide (KI) Radioiodides OTC SNS Prussian Blue Cesium Thallium Rx SNS

* SNS is the Strategic National Stockpile

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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 place

p

• External decontamination
• Consider irrigation cathartics and

Consider irrigation, cathartics and laxatives

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AFRRI

Topics Topics

Acute Radiation Syndrome (ARS) Acute Radiation Syndrome (ARS)

• Definition and diagnosis
• Treatment

Treatment External and Internal Contamination

• Definition and diagnosis
• Treatment

Examples, Follow-Up Care, Research Areas

E l f M di l R Examples of Medical Response to Radiation Accidents

• 1986 Chernobyl, Ukraine (former USSR)
• 1987 Goiânia, Brazil
• 1999 Tokaimura, Japan

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CHERNOBYL

April 1986 Worst Radiation Accident in History in History

Photo: Monitoring Chernobyl Photo: Monitoring Chernobyl Reactor from Helicopter

Adapted from AFRRI

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Chernobyl M di l R Medical Response

• 500 personnel hospitalized

– > 100 personnel received > 1 Gray p 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.

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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 Death

Causes of Death

– Burns 5 – Interstitial pneumonitis 3 – Graft versus Host Disease 2 – Renal failure & ARDS 1 11 deaths 11 deaths

• Conclusion: No clear evidence that bone marrow

transplants were beneficial transplants were beneficial

Gale et al, NEJM, 1989; 321: 205-212 / UNSCEAR 2000 Appendix J.

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Chernobyl at 20+ Years Chernobyl 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 mentality Victim mentality – Expecting medical problems – Socio-economic problems p

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Chernobyl Forum, 2005.

Goiânia, Brazil, September 1987

“ Worst radiation accident in in the Western Hemisphere” p

Science, 1987

Source:

Science, 1987

~ 2.5 cm diameter ~ 1400 Ci, Cesium-137 as CsCl salt (powder) as CsCl salt (powder)

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Adapted 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 d contaminated

• 20 (0.01%) required

t t t treatment

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IAEA Pub “The Radiological Accident in Goiania”, 1988 available 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

• Treatment

Chelation therapy: Prussian Blue py Infection/sepsis: antibiotics, antifungal, antiviral Bone marrow stimulation: GM-CSF

• Outcome:

4 deaths (4-6 Gy)

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IAEA Pub “The Radiological Accident in Goiania”, 1988 available at www-pub.iaea.org

Tokaimura, Japan 1999

Incident: Criticality accident

B B A A

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Endo & Yamaguchi, Radiat Res 159, 2003.

Tokaimura, Japan: P ti t A Patient 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 impairment intestinal, renal and respiratory impairment

• Numerous problems with vascular

hyperpermeability hyperpermeability

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Adapted from AFRRI

Patient A Interventions Patient 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

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Adapted from AFRRI

Tokaimura, Japan: P ti t B Patient 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

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Adapted from AFRRI

Patient B Interventions (contd) Patient B Interventions (contd)

• Severe cutaneous burns required multiple

skin grafts

• Developed radiation pneumonitis and

pulmonary hemorrhage pulmonary hemorrhage

• Expired 7 months after incident in April 2000

Expired 7 months after incident in April 2000

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Adapted from AFRRI

Long Term and Follow-Up Care Long Term and Follow Up Care

• Multiple Organ Dysfunction: pulmonary,

p g y p y hepatic, renal and cardiac failure

• Possible late effects

Possible late effects

– Malignancies: Leukemia early, then breast, intestinal, lung, thyroid etc. , g, y – Cataracts, sterility – In-utero and childhood effects In utero and childhood effects – Psychosocial

• Need long term screening
• Need long term screening

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Research Areas Research 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 Contamination D fi i i d di i

• Definition and diagnosis
• Treatment

Examples, Follow-Up Care, Research Areas

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Questions?