# Presentation: 498865

## Diagnosis ,Treatment and Medical   Effects of Radiation ContaminationAlbert 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

## OBJECTIVES

- Discuss external contamination and the body’s mechanisms for the internalization of radionuclides.
- Discuss the procedures for diagnosis ,treatment and effects of internal contamination with radionuclides.

## 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 victim’s 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.

## Patient Arrival

- Determine priorities:
- Is patient stable?
- Manage life threatening problems _first_.
- Is patient contaminated?
- Remove patient’s clothing, blankets, sheets.
- Place in plastic bag.
- Change gloves.

## Collect Samples from:

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

## V.  Decontamination

- 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

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

## 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.

## Whole-body Absorption Fractions of 58CoCl2 through mechanically wounded and damaged skin

## 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

## 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)

## 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

## There is inhalation risk  from a  variety of incidents causing a radionuclide plume.

## e

| Elicited Risk 1 | 10 |
| --- | --- |
| BEIR V 2 | 8 |
| ICRP 60 | 12 |
| UNSCEAR 1994 | 12 |
| UNSCEAR 20003 | 9 |

**e**

**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)***_

**1****Elicited 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)**

## 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

## Internal dosimetry necessary for medical management

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

## 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 ALI’s 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

## Some ALI’s 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

## 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.

**Notes:**
Assessment techniques include whole-body or wound counting and urine/fecal bioassay.

## 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!**

## Bioassay Is Necessary for Diagnosis/Monitoring,but Has Limitations

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

## 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

## Lung Counting with Phoswich Detector Used to Dx/Monitor IC

## 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.

**Notes:**
At the instructor’s discretion, dynamics of particle deposition in the tracheo-bronchial tract will be discussed.

## Particle Size Distribution in the Respiratory Tree

**18-20**
**15-18**
**7-12**
**4-6**
**(bronchioles)**
**1-5  (alveoli)**

- Particle Size (Micron, Mass Median Diameter)

**Notes:**
AEROSOL INFECTIVITY AND RELATIVE PARTICLE SIZE

The most effective delivery method for BW infection is by the inhalation of an aerosol containing biological agent particles that are in the 1 to 5 micron size range. Particles in this size range behave similar to a gas and can be taken into the end bronchioles and alveoli during normal respiration. Larger sized particles either quickly fall out of the biological aerosol or they become trapped in the upper airway. Smaller sized particles are breathed into the lung, but expired out again without retention. The realization of this optimum particle size / infectivity ratio was a major advance in the development of offensive biological warfare.
The first BW agents were manufactured as wet slurries of highly concentrated bacterial and viral agents. These slurries were easy and relatively safe to manufacture but were difficult to disseminate in the correct particle size range and had to be refrigerated for storage. After the discovery of the particle size / infectivity relationship, the next significant advance in biological warfare was the development of biological agents in freeze-dried powder formulations. Although these were technically difficult and dangerous to manufacture, their low refrigeration requirement, ease of dissemination, and high concentration of infectious agent, made them suitable for a variety of covert, tactical, and strategic uses.

## Clearance Time - Nasopharynx

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

## Clearance Time of Respiratory Tract

- 							**Hours**
- Trachea					      .1
- Bronchi					    1.0
- Bronchioles				    4.0
- Terminal Bronchioles		   10.0
- Alveoli					  100.0 Days+

## Uptake of Actinides(Pu,Am,Cf,etc) May Be Remarkably Rapid

**Bone**
**Deposition**

**Time (Hours)**

**0**

**1**

**2**

**100**

**80**

**60**

**40**

**20**

**0**

**Percent Deposited**

## 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

## 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

## Saturate the Critical Organ with the Stable Isotope

**Saturate the Critical Organ with the Stable Isotope**

**THYROID**

**131****I**

**131****I**

**131****I**

**131****I**

- I

## Prompt KI Treatment of 131I Intake is Highly Effective

** ****0**

**15**

**30**

**6**

**12**

**18**

**24**

**Time of administration**
** ****post-exposure, hours**

**Thyroid Uptake, %**

## Health Effect:Childhood 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.

## FDA Recommendations for Potassium Iodide

- A daily dose of:
- 16 mg of KI for infants <1 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

## Clearance Time of Gastrointestinal Tract

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

## 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**

## Absorption of Ingested Radionuclides

**    ****GROUP****	****	****ELEMENTS     ****	****%ABSORBED**
**Lanthanides****	****	****   Ce,**** ****Pm,****	****	****	****<0.1**
**	****	****	****     ****Eu,**** ****Tb**
**Actinides****	****	****     ****Th,**** ****U,****	****	****	****<0.1**
**	****	****	****    ****Np,**** ****Pu****	**

## Reduction of Absorption From Gastrointestinal Tract

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

## Medical Countermeasures Are Generally  Element Specific

- 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 |

## Isotopically Dilute

**Men**

**BEER**

**TRITIUM**

## Displace

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

## 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 dosage__:_*Adults:* 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.

## V.  Decontamination

- 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

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

## Excretion of Inhaled Uranium

## Chelators

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

## 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**

## 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**

## 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®)

## 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.

## 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**

## 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 < 1 ALI, no treatment.
- For 1< intake < 5 ALI, possibly no treatment, with physician discretion.
- For 5 < intake < 10 ALI, consider treatment.
- For intake >  10 ALI, probably treat ,with patient consent.
- We need consenus on a mass casualty plan! management plan.

## Cs-137 Inhalation  INTAKE:WHAT 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.

## Example:Assume 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???

## 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 patient’s risk perception, MD can decide on Rx.

## Example:One 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% > liver, 10% > kidney, 10% > red marrow, 10% > 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.

## 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!

## 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

## 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)

## More Good References

- _[www.orau.gov/REACTS](http://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

## Thank you!wileya@orau.gov