Diagnosis ,Treatment and Medical Effects of Radiation Contamination Albert L. Wiley,MD,PhD,USNR(RET) Dir., REAC/TS and WHO REMPAN Ctr.,Oak Ridge

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Diagnosis ,Treatment and Medical Effects of
Radiation ContaminationAlbert L.
Wiley,MD,PhD,USNR(RET)Dir., REAC/TS and WHO
REMPAN Ctr.,Oak Ridge
Oak Ridge Regional Emergency Management
Forum Emergency Management-Preparing the
Community October18,2007
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OBJECTIVES

• Discuss external contamination and the bodys
  mechanisms for the internalization of
  radionuclides.
• Discuss the procedures for diagnosis ,treatment
  and effects of internal contamination with
  radionuclides.

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External Contamination

• Most contamination will be on clothes. At least
  outer clothing should be removed before transport
  of patient to hospital (to minimize spread of
  contamination to ambulance and ED).
• Send victims identification (in plastic baggie)
  to the ED with the victim.
• As much as possible, leave contaminated materials
  (including the clothes that were removed) at the
  incident scene.

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Patient Arrival

• Determine priorities
• Is patient stable?
• Manage life threatening problems first.
• Is patient contaminated?
• Remove patients clothing, blankets, sheets.
• Place in plastic bag.
• Change gloves.

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Collect Samples from

• Nose
• Mouth
• Wounds
• Also Baseline urine, then 24-hour samples of
  urine and feces

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V. Decontamination

• Determine priorities
• Consider
• Medical needs of patient
• Chemical nature of contaminant
• Seriousness and extent of contamination
• Presence of wounds

• Key Issues
• Clothing removal if not accomplished
• Radiological survey documentation
• Collection of samples specimens
• Prioritize decon effort
• open wounds
• body orifices
• intact skin
• Type of decon procedure documentation
• Radiological reassessment documentation

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Decontamination Intact Skin

• 1. Wash with water.
• 2. Use the mechanical action of flushing and/or
  friction of cloth, sponge or soft brush.
• 3. Begin with the least aggressive techniques and
  the mildest agents.
• 4. For showering, begin with the head and proceed
  to the feet.
• 5. Keep materials out of eyes, nose, mouth and
  wounds. Use waterproof draping to limit spread.
• 6. Avoid causing mechanical, chemical or thermal
  damage to skin.

• Helpful hints
• Drape clean areas.
• Wipe toward center
• Blot to dry.
• Provide privacy for patient.
• Remember GRAVITY.

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Whole-body Absorption Fractions of 58CoCl2
through mechanically wounded and damaged skin
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DOE Summary of Dose Limits for Radiation
Workers

• Whole Body (int ext) - 5 rem/yr
• occupational exposure
• Lens of Eye -15 rem
• Extremities - 50 rem
• Organ, tissue, skin - 50 rem
• Declared pregnant - 0.5 rem
• gestational period
• Minors under 18 yrs - 0.1 rem
• General public - 0.1 rem

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Internal Contamination Defined

• The presence of radioactive material inside the
  body.
• Excludes normal background levels of
  radioactivity in the body
• Usually considered of medical urgency, but seldom
  acutely life-threatening (stochastic risk is the
  usual dominant risk, although deterministic risk
  can occur and even be lethal ,as in recent
  Polonium 210 incident in UK.)
• Treatment can be effective, but is ELEMENT
  specific (so,need early isotope identification)

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Common Routes of Entry

• Inhalation (usually most important)
• Ingestion
• Injection (wound)
• Absorption through intact or abraded skin
• Intact skin is an effective barrier against
  almost all radionuclides
• burned skin may be more permeable to
  radionuclides than intact skin

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There is inhalation risk from a variety of
incidents causing a radionuclide plume.
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Estimate of total cancer risks for a population
(European Union/US) exposed to high dose/dose
rate Low-LET radiation -- Risks/100
persons/Sv (data abstracted from Table 38 UNSCEAR
2000)
e
Elicited Risk 1 10
BEIR V 2 8
ICRP 60 12
UNSCEAR 1994 12
UNSCEAR 20003 9
1Elicited estimate from poll of experts 2A-Bomb
follow-up through 1985 3A-Bomb follow-up through
1990 (for low dose/dose rate exposures, risk is
lower by 1/2)
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ICRP 26 Dose Limits(1977--1985)

• Three principles of radiation protection
• justification, limitation, optimization
• Recommended Limits
• stochastic effects 50 mSv (5 rem) per year
• non-stochastic effects 500 mSv (50 rem) per
  year, but 150 mSv to eye lens (3 mm)
• declared pregnant woman 5 mSv
• Also recommended Q 20 for neutrons

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Internal dosimetry necessary for medical
management

• Disciplines
• Physics
• Chemistry
• Mathematics
• Anatomy
• Physiology
• Radiobiology
• Industrial Hygiene

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Annual Limit on Intake (ALI)Used to Acess Risk--
and ? Decision for Start/Stop Treatment

• Defined as the dose limit divided by the dose
  conversion factor
• Dose limit may be either stochastic (SALI) or
  non-stochastic (NALI)
• Different ALIs for inhalation and ingestion
• Only one significant figure
• Example Cs-137
• 0.05 Sv/8.6 x 10-9 Sv/Bq 6 x 108 Bq

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Some ALIs of Interest in Microcuries

• Radionuclide ALI (inhalation) ALI (ingestion)
• H-3 80,000 80,000
• P-32 400 600
• Co-60 30 200
• Sr-90 4 400
• Cs-137 200 100
• Ra-226 0.6 2
• U-238 0.8 200
• Pu-239 0.006 0.8

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Methods for Assessing Intakes

• Whole Body Counting
• Feasible for nuclides that emit penetrating x or
  gamma rays.
• Useful also for nuclides emitting energetic beta
  particles - can be detected by their
  bremsstrahlung radiation.
• Bioassay
• Urine - most widely used.
• Feces.
• Excised material from wounds.
• Chromosome aberration analysis.

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Immediate Diagnosis/Emergency Intake Estimates

• Nasal Swabs
• Facial surveys
• Sputum
• Spot urine (Sometimes useful,ie,Cs)
• ? Deployable lung counters
• When all else fails - get a good history!

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Bioassay Is Necessary for Diagnosis/Monitoring,bu
t Has Limitations

• 1. Slow
• 2. Usually need collections of both urine and
  feces
• 3. May overestimate uptakes
• 4. Expensive

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Methods for Assessing Intakes

• Whole Body or Lung Counting
• Feasible for nuclides that emit penetrating x or
  gamma rays.
• Useful also for nuclides emitting energetic beta
  particles - can be detected by their
  bremsstrahlung radiation.
• Bioassay
• 24 hr Urine collections - most widely
  used(liquid scintillation and spectroscopy)
• 24 hr Feces collections
• Excised material from wounds.
• Cytogenetic Biodosimetry

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Lung Counting with Phoswich Detector Used to
Dx/Monitor IC
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Inhalation Pathway(Importance of Particle Size
and Chemical Form)

• Particle size of the aerosol particles determine
  region of the respiratory tract where most are
  deposited.
• Fate of inhaled particles is dependent on their
  physico-chemical properties.
• Highly insoluble particles remain in the lung for
  longer periods of time than soluble compounds.
• A small fraction will be transported to the
  tracheo-bronchial lymph nodes by pulmonary
  macrophages.
• Some are cleared through the airways, swallowed,
  and excreted in the feces.

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Particle Size Distribution in the Respiratory Tree
Particle Size (Micron, Mass Median Diameter)
18-20 15-18 7-12 4-6 (bronchioles) 1-5
(alveoli)
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Clearance Time - Nasopharynx

• Time to Swallowing
• Anterior Nares 60 min.
• Nasopharynx 10 min.
• (10 mm/min)

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Clearance Time of Respiratory Tract

• Hours
• Trachea .1
• Bronchi 1.0
• Bronchioles 4.0
• Terminal Bronchioles 10.0
• Alveoli 100.0 Days

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Uptake of Actinides(Pu,Am,Cf,etc) May Be
Remarkably Rapid
100
80
Percent Deposited
Bone Deposition
60
40
20
0
0
1
2
Time (Hours)
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Dose Inhalation Pu-239

• Type S material
• Lung highly irradiated organ
• Effective dose reflects lung dose
• Dose rate for systemic tissues increase to broad
  maximum value at about 6000 d

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Pu-239 Inhalation

• Integrated dose rate as a function of time
• Integral converged for lung and effective dose
• Bone surface and liver integral not converged

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Saturate the Critical Organ with the Stable
Isotope
131I
131I
I
THYROID
131I
131I
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Prompt KI Treatment of 131I Intake is Highly
Effective
0
Thyroid Uptake,
15
30
6
12
18
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Time of administration post-exposure, hours
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Health EffectChildhood Thyroid Cancer near
Chernobyl from I-131

• In Gomel region of Belarus, north of Chernobyl,
  children were screened for thyroid cancer by
  physical examination, ultrasound imaging of the
  thyroid, and by thyroid function tests.
• Prior to the accident, thyroid cancer rate
  0.5/million. In the period 1991-1994, rate
  96.4/million. This represents almost a 200-fold
  increase.
• Reference BMJ, vol 310, p 801, March 25, 1995.

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FDA Recommendations for Potassium Iodide

• A daily dose of
• 16 mg of KI for infants lt1 month
• 32 mg of KI for children 1 month to 3 years
• 65 mg of KI for children and teenagers 3 years to
  18 years
• 130 mg of KI for adults including pregnant and
  lactating women and adolescents over 150 pounds
• Daily dosing should continue until the risk of
  exposure has passed and/or until other measures
  (evacuation, sheltering, control of the food and
  milk supply) have been successfully implemented

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Clearance Time of Gastrointestinal Tract

• Occupancy Time
• (Hours)
• Stomach 6
• Small Intestine 14
• Upper Large Intestine 18
• Lower Large Intestine 22

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Absorption of Ingested Radionuclides

• GROUP RADIOACTIVE ABSORBED
• ELEMENTS OF
• Alkali Metals Na, K, High 90
• Rb, Cs
• Group VIII Fe 10
• Metals Co 30-90
• Ru 3

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Absorption of Ingested Radionuclides

• GROUP ELEMENTS ABSORBED
• Lanthanides Ce, Pm, lt0.1
• Eu, Tb
• Actinides Th, U, lt0.1
• Np, Pu

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Reduction of Absorption From Gastrointestinal
Tract

• 1. Antacid
• 2. Precipitation into insoluble salt
• 3. Catharsis

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Medical Countermeasures Are Generally Element
Specific
Nuclide Medication Comments
Am-241 Ca and Zn DTPA by IV, aerosol,?IM Clelation,Works on liver even after long deposition
Cf-252 Ca and Zn DTPA
Cs-137 Prussian Blue Binds Cs,hepato-enteric cycle
Co-60 penicillamine Gastric lavage,?DTPA
Fission Products Depends on mixture Spectroscopic identificationnuclides isotope,specific RX
H-3 Forced H2O Isotopic dilution
I-131 KI or SSKI Give in first 1-6 hours
P-32 Phosphates Isotopic dilution
Pu-239 Ca and Zn DTPA EDTA less effective
Sr-89/90 Sr,Ca gluconate,iv Consider alginates
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Isotopically Dilute
BEER
Men
TRITIUM
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Displace

• USE CALCIUM TO COMPETE WITH RADIOSTRONTIUM
• USE STABLE IODIDE TO COMPETE WITH RADIOTECHNETIUM

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Uranium

• Chemical toxicity to kidney is usually the main
  issue. Radiotoxicity is significant only with
  enriched U-235.
• TREATMENT
• Sodium bicarbonate to alkalinize urine
• Oral dosageAdults Initially, 4 g PO then 1-2 g
  every 4 hours. Titrate dosage based on urinary
  pH.Children 1-10 mEq/kg/day (84-840 mg/kg/day)
  PO, given in divided doses every 4-6 hours.
  Titrate dosage based on urinary pH.
• May need renal dialysis until renal recovery from
  injury.

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V. Decontamination

• Determine priorities
• Consider
• Medical needs of patient
• Chemical nature of contaminant
• Seriousness and extent of contamination
• Presence of wounds

• Key Issues
• Clothing removal if not accomplished
• Radiological survey documentation
• Collection of samples specimens
• Prioritize decon effort
• open wounds
• body orifices
• intact skin
• Type of decon procedure documentation
• Radiological reassessment documentation

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Excretion of Inhaled Uranium
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Chelators

• DTPA - Diethylenetriaminepentaacetic Acid
• EDTA - Versene
• BAL - Dimercaprol
• DFOA - Deferoxamine
• PCA - Penicillamine

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Prompt DTPA Treatment of 239Pu Intake is Highly
Effective

• Retention ( of Uptake)
• Control DTPA Treated
• Liver 14.0 0.47
• Skeleton 57.0 5.9

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How to Administer DTPA

• IV injection of DTPA (1 gm/4ml) with 6 ml saline
  over 5-10 minutes
• IV Piggyback (1 gm DTPA in 100ml saline) over 20
  minutes
• Aerosol 1 gram undiluted via hand-held
  nebulizer inhalation takes 10-15 minutes
• IM injection (painful)
• Under 18 YOA, use zinc-DTPA
• Monitor magnesium and other electrolytes
  routinely
• Complete package information available at
• www.orau.gov/reacts/resources.htm

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REAC/TS DTPA Program

• Maintain Registries of DTPA and PB use in US
• Provide a stock of pharmaceuticals at REAC/TS and
  with co- investigators for treatment of internal
  contamination
• Ca- and Zn-DTPA
• Prussian Blue (Radiogardase)

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REAC/TS Deployment Teams SPECIAL Medical
Responsibilities

• REACTS provides 24/7 response for on site
  medical care to NNSA assets (FRMAC, etc.) with
  additional special responsibility/capability to
  provide rapid deployment for radiation dose
  estimate and emergency treatment of INTERNAL
  contaminations with DTPA, Prussian Blue.

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Prussian Blue is Effective in Rx of Radio-Cesium
or Thallium Uptake

• Binds ions in gut
• Reduces biological half life and may avert Cs137
  dose(CEDE) to approx one third of untreated value
• Not absorbed,relatively non-toxic-monitor K
• Reduces recycling
• Need to monitor urine,feces during Rx
• First used effectively for Cs in Brazil
  accident,1987.
• Complete package information available at
  www.orau.gov/reacts/resources.htm

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Who/When to Treat?(Guidelines for Industrial
Accidents)

• ALI (annual limit of intake) is that CEDE
  necessary to give 5 rem 0.05 Sv.
• For intake lt 1 ALI, no treatment.
• For 1lt intake lt 5 ALI, possibly no treatment,
  with physician discretion.
• For 5 lt intake lt 10 ALI, consider treatment.
• For intake gt 10 ALI, probably treat ,with
  patient consent.
• We need consenus on a mass casualty plan!
  management plan.

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Cs-137 Inhalation INTAKEWHAT IS THE DOSE
(CEDE)?
Step 1) Estimate the Intake Using Intake
Retention Fractions.
At 190 days about 18 of Cs-137 Remains in whole
body.
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ExampleAssume Lung Counts Measured 1.48 MBq
40 uCi of Cs-137 at 190 Days
Intake (Inhalation) 1.48 MBq/0.18 8.2 MBq 40
uCi/0.18 222 uCi
Step 2) Compare to Annual Limit on Intake
(ALI). ALI 7.4 MBq 200 uCi for Cs-137
(Gives 0.05 Sv 5 rem CEDE) So individual has
110 of ALI and Dose of 0.55 Sv 5.5
rem! TREAT???
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Bioassay Example of Urine Data Used to Decide on
Rx

• A worker spends some time in an area where Co-60
• (T1/2 5.271 y) oxide is present. At the end
  of the quarter (70 days later), activity is
  detected in his routine urine sample. Follow-up
  samples reveal the following excretion pattern
• Days after
  24-hour urine
• suspected exposure activity (Bq)
• 70
  60
• 100
  50
• 130
  45
• A lung count on day 70 revealed 0.25 MBq of
  Co-60.
• Using IRF and DCF ,can calculate organ
  doses--then,based on regulations and patients
  risk perception, MD can decide on Rx.

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ExampleOne Data-Point Organ Dose Estimates for
UK Po210 Incident

• Per ICRP 68, 10 of soluble Po-210 is absorbed
  from the GI tract (of that 30 gt liver, 10 gt
  kidney, 10 gt red marrow, 10 gt spleen, remainder
  distributed in soft tissue)
• Hypothetical Data point Suppose a bioassay on
  Nov 22 suggested 1 GBq (27 mCi) of Po-210 in the
  whole body. Correcting for the effective(bio and
  physical) half-life, this would have been 1.5
  GBq on Nov. 1, resulting from an estimated intake
  of 15 GBq, or 0.09 mg.

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One Data-Point Po210 Organ Dose Estimate,
Example(cont)

• The initial dose rate to red marrow would be
• (1.5 GBq x 0.1 x 5.3 MeV x 1.609E-13 J/MeV)/1.5
  kg 8.5 mGy/sec
• 8.5 mGy/sec x 3600 x 24 74 Gy (7400cGy) per
  day. After 22 days, this would have decreased to
  49 Gy/d. The integrated dose to red marrow would
  be 1300 Gy.
• Similarly, the initial dose rates to liver would
  be 185 Gy/d, to kidney 335 Gy/d, and to spleen
  306 Gy/d. The integrated doses to these organs
  would be 3220, 5830, and 5320 Gy, respectively.
• Sometimes Treatment Decision is Clear!

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Internal Contamination Summary

• Intakes of radionuclides can be treated
  successfully
• The appropriate treatment is element-specific, so
  the contaminant must be identified
• The sooner treatment is begun, the better
• Reference NCRP Pub. 65, Management of Persons
  Accidentally Contaminated with Radionuclides

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Good References!

• NCRP 65 Management of Persons Accidentally
  Contaminated with Radionuclides (April, 1980)
• EPA Federal Guidance Report 11 Limiting Values
  of Radionuclide Intake and Air Concentration and
  Dose Conversion Factors for Inhalation,
  Submersion and Ingestion (EPA-520/1-88-020,
  Sept., 1988)

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More Good References

• www.orau.gov/REACTS (Detailed video demonstration
  of external decontamination)
• Ca/Zn DTPA Package Insert,FDA website
• Prussian Blue Package Insert,FDA website
• KI Package Insert,FDA website

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Thank you!wileya_at_orau.gov