Centre for Radiation, Chemical and Environmental Hazards

Triage, Monitoring And Dose Assessment For People Exposed To Ionising Radiation Following A Malevolent Act

Radiological and Nuclear Emergency Management: Aspects of Radiobiology

ENEA Casaccia Research Centre, Rome

6 November 2012

George Etherington, Kai Rothkamm, Arron Shutt and Mike Youngman

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Outline

• Objectives of triage and monitoring

• Scenarios

• Current challenges

• Assistance networks

• International projects

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Objectives of individual monitoring in emergencies

1. To quantify absorbed doses to organs for people who may be at risk of deterministic effects on their health (e.g. acute radiation syndrome)

• providing an input to decisions on medical treatment

2. To quantify effective doses for people exposed at lower levels but still potentially at risk of stochastic effects on their health (cancer induction)

• providing an input to decisions on “decorporation” (e.g. use of Prussian Blue for radiocaesium intakes)

3. To identify the potentially large numbers of people for whom exposures are unlikely to have an effect on health

• e.g. the “worried well”

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Malevolent use scenarios

• An external irradiation incident (e.g. “hidden source”)

• An environmental contamination incident (e.g. a radiological dispersal device, RDD)

• A food/water contamination incident

http://www.tmthandbook.org

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Malevolent use scenarios

• Any incident would occur at a location not known in advance (therefore, no site-specific plans)

• The location could be a highly populated urban area• Large numbers of people could be affected• The time between exposure and detection of the

incident may be unknown (covert scenarios)• Radiation exposures could range from very low to

substantial, and could be combined with conventional injuries

Factors to be taken into account

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C1. Rapid selection and prioritisation of people for monitoring

C2. Rapid initiation of individual contamination monitoring atthe scene

C3. Monitoring large numbers of peopleC4. Monitoring: different people, different detection systemsC5. Monitoring for contamination by α- and pure β-emittersC6. Rapid determination of external irradiation dosesC7. Rapid interpretation/assessment of individual

contamination monitoring dataC8. Evaluation of internal dose thresholds for deterministic

effects

Some major challenges

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The use of simple procedures for rapidly sorting people into groups based on:

- their degree of physical injury

- actual or potential effects on health

and the allocation of “care” to these people so as to expedite treatment and maximise the effective use of resources.

Trauma triage

Radiological triage

Rapid selection and prioritisation for monitoring C1

The concept of “Triage”

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Types of “care”

The term “care” is used in a broad sense, for:

• urgent treatment of trauma injuries • treatment of life-threatening radiation exposures• decontamination procedures

through to

• radiological monitoring designed to provide information and reassurance

• provision of advice on possible health consequences

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Radiological triage stages

0 1 2 3 4 5 6Time period after incident (d)

(Trauma triage)

Clinical observations

Information on location, proximity

Biodosimetry

Initial contamination screening measurements

Measurements with transportable body monitors

Measurements with laboratory body monitors

Results of urine monitoring

Monitoring

Pre-monitoring

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Triage at Goiânia

0.00011Severe trauma (amputation)

0.00044Deaths

0.00222People needing intensive medical care

0.00549People admitted to hospital

0.025249People with significant external and internal doses

11112,000People monitored

100~ 1,000,000Total population

% of populationNumberGroup

0.00011Severe trauma (amputation)

0.00044Deaths

0.00222People needing intensive medical care

0.00549People admitted to hospital

0.025249People with significant external and internal doses

11112,000People monitored

100~ 1,000,000Total population

% of populationNumberGroup

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Rapid initiation of contamination monitoring C2

External contamination monitoring

“Pre-monitoring” triage

Rapid screening for internal contamination

Measurement of internal contamination

Decontamination

External contamination monitoring

“Pre-monitoring” triage

Rapid screening for internal contamination

Measurement of internal contamination

Decontamination

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Rapid initiation of contamination monitoringMonitoring large numbers of peopleC2, C3

Measurement of internal contamination

Screening(triage)

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Monitoring large numbers of people

HPA’s transportable body monitoring system

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Monitoring: different people, different detectors C4

Monte Carlo particle transport calculations for body monitoring

Problems:- In a radiological incident, members of the general public are not

well-represented by standard calibration phantoms. - A wide range of detectors may need to be used.

Aim: To allow body monitoring calibrations for any possible detector system, radionuclide, age, subject size and orientation.

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Modelling of mathematical detector/phantom system

Schematic

Comparison between mathematical

and physical calibration

Model

MCNPX

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Monitoring for contamination by α- and pure β-emitters C5

Issues- People need to be given instructions on providing samples that can be followed reliably- Ideally, 24 hour urine samples are needed- Reliable arrangements for sample collection & delivery to laboratory are needed- A reliable sample tracking system is needed - Sample preparation and radiochemistry are likely to be time-consuming- Sample throughput can be quite low

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Rapid determination of external irradiation doses C6

• Biologically-based biodosimetry• Physically-based biodosimetry• Dose estimation based on clinical observations

Swartz HM et al (2010). Health Physics 98, no 2, 95-108

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Biologically-based biodosimetry

Measurements of biological materials/processes affected by radiation exposure

Examples:• chromosome damage [dicentrics, micronuclei, translocations, PCC] IAEA (2011)• gene expression signatures Paul et al (2008)• protein biomarkers

– C-reactive protein (CRP) [acute phase inflammatory response, useful up to 3 d after exposure; dose > 1 Gy; reproducibility?] Blakely et al (2010)

– γ-H2AX [DNA damage signalling & repair; useful up to 2d after exposure, radiation-specific; sensitive to doses > 200 mGy; results within 24 h] Rothkamm & Horn (2009)

- Chromosome aberration analysis is the “gold standard”, but time-consuming and low throughput; some gains possible through automation

- Few methods are completely specific to radiation damage- Complex time-dependent responses, often short-lived- Gene expression & protein biomarkers – great potential but not validated - Most assays are not field-deployable – specialised laboratories needed

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Physically-based biodosimetry

Measurements of physical effects in tissues after radiation exposure

Examples:• Free radicals in finger nails measured by Electron Paramagnetic

Resonance (EPR)• Radiation-induced defects in tooth enamel measured by EPR or

Optically-Stimulated Luminescence (OSL)Health Physics 98, no 2 (2010)

- Effects are generally specific to radiation damage- Some techniques show time-independent response (e.g. EPR on tooth

enamel)- Potentially field-deployable- OSL can also be used with personal electronic devices (chips, CCs, etc.)

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Dose estimation based on clinical observations

Clinical observations and haematology measurements after radiation exposure Goans & Waselenko (2005)

Examples:• Time to onset of nausea & vomiting• Serial lymphocyte counts• Neutrophil:lymphocyte ratio measurement

- Effects not necessarily caused by radiation exposure- Haematology measurements require skilled personnel and repeated

blood sampling

Concentration of blood lymphocytes, μl-1

(Dainiak, 2007).

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Rapid interpretation of individual contamination monitoring data C7

200 mSv

20 mSv

1 mSv

Upper level

Lower level

Dual Action Level approach

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Upper Action Levels on dose

Internal contamination• E50 = 200 mSv

• Level proposed by TIARA project above which medical treatment to reduce doses (e.g. by decorporation) should be considered (Menetrier et al., 2005)

External contamination• D = 2 Gy to skin

• 20% of the level recommended by IAEA (Generic Procedures for Medical Response (IAEA-EPR-MEDICAL 2005)) for immediate decontamination, immediate medical examination, and medical treatment.

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Upper Action Levels on dose

Example: 60Co inhalation (adults)

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Actions associated with Action Levels

M > ALU (upper action level)• urgent external decontamination (if appropriate)• refer for immediate medical assessment• take blood samples for serial lymphocyte counts• … and for biodosimetry measurements

ALU > M > ALL (upper action level)• external decontamination in priority order (if appropriate)• more accurate internal contamination measurements in priority order• long-term follow-up monitoring

M - measurementALU – upper action levelALL – lower action level

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TIARA method: 137Cs whole body measurement

TIARA – Treatment Initiatives after Radiological Accidents (Menetrier F et al., 2007)

137Cs whole body measurement

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Rapid assessment of internal doses C7

Dose per unit measurement “look-up“ tables

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Limitations on use of “look- up”dose assessment tables

Calculations use a combination of default parameter values, BUT

• Particle size distribution could be highly variable

• Absorption Type is dependent on chemical form, on which information would be sparse

• Intake pathway may be uncertain

• Measurements (particularly rapid screening measurements) could have large uncertainties

Therefore, while dose assessments based on default values for input data may be adequate for initial dose assessments …

… they may not be adequate as a final assessment if doses are significant

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Evaluation of internal dose thresholds for deterministic effects C8

IAEA (2005). Generic Procedures for Medical Response during a radiological or nuclear emergency, EPR-Medical 2005

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Effect of dose protraction

Example: Risk of mortality vs bone marrow dose

0.00

0.20

0.40

0.60

0.80

1.00

0 2 4 6 8 10

Absorbed dose (Gy)

Ris

k

1 Gy/h

0.02 Gy/h

NRPB (1996). Risks from Deterministic Effects of Ionising Radiation.

Risk = 1 – exp(-H)H = ln 2 (D/D50)V

H – hazard functionD – absorbed doseV – shape factor

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Plans for triage and monitoring for people returning to the UK after Fukushima

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International Networks

IAEA Response Assistance Network (RANET)coordinates international assistance in the event of a radiationemergency (specialist laboratories, monitoring, data analysis, modelling). http://www-pub.iaea.org/MTCD/publications/PDF/Ranet2010_web.pdf

WHO BioDoseNeta worldwide biological dosimetry network to complement smaller local networks in the event of large numbers of casualtieshttp://www.who.int/ionizing_radiation/a_e/biodosenet/en/index.html

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Network-related projects

RENEB“Realising a European Network of Excellence in Biological Dosimetry”. EC-funded project to realise the European Network of Biodosimetry, 2012 - 2015. http://www.reneb.eu

Global Health Security Initiative (GHSI)an international forum to share and collaborate on initiatives to enhance global public health preparedness

Radiological / Nuclear Threats Working GroupSurvey/database of radionuclide bioassay laboratory capabilities. Aims are to establish an international radionuclide bioassay laboratory network; develop standard procedures; hold emergency exercises

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Other networks / projects

EURADOS WG7aims to harmonize and co-ordinate research in internal dosimetry and to disseminate scientific knowledge. http://eurados.org

EURADOS WG10aims to establish a multi-parameter approach to dose assessment in retrospective dosimetry, spanning both biological and physical dosimetry and including emergency response. http://eurados.org

MULTIBIODOSE“Multi-disciplinary biodosimetric tools to manage high scale radiological casualties” http://www.multibiodose.euEC FP7 Security Research Programme project (currently in 3rd year)

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References

TMT Handbook (2009). Triage, Monitoring and Treatment of People exposed to Ionising Radiation following a Malevolent Act. CarlosRojas-Palma, Astrid Liland, Ane Naess Jerstad, George Etherington, Maria del Rosario Pérez, Tua Rahola and Karen Smith (editors). http://www.tmthandbook.org

HPA (2010). Use of Prussian Blue (Ferric Hexacyanoferrate) for Decorporation of Radiocaesium). Advice from the Health Protection Agency. Radiation, Chemical and Environmental Hazards RCE-17, December 2010. http://www.hpa.org.uk/Publications/Radiation/DocumentsOfTheHPA/

Etherington G, Rothkamm K, Shutt A L and Youngman M J (2011). Triage, monitoring and dose assessment for people exposed to ionising radiation following a malevolent act. Radiat Prot Dosim 144, 534-539.

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Biodosimetry references

Swartz HM et al (2010). A critical assessment of biodosimetry methods for large-scale incidents. Health Physics 98, no 2, 95-108.

Blakely WF et al (2010). Multiple parameter radiation injury assessment using a non-human primate radiation model – biodosimetry applications. Health Physics 98, no 2, 153-159.

Rothkamm K and Horn S (2009). Ann Ist Super Sanità 2009 45 no 3, 265-271.

Goans RE & Waselenko JK (2005). Medical management of radiological casuatlies. Health Physics 89, no 5, 505-512.

Paul S & Amundson SA (2008). Development of gene expression signatures for practical radiation biodosimetry. Int J Radiat Oncol Biol Phys 71, no 4, 1236–1244.

IAEA (2011). Cytogenetic Dosimetry: Applications in Preparedness for and Response to Radiation Emergencies. EPR-Biodosimetry 2011.

Centre for Radiation, Chemical and Environmental Hazards

Triage, Monitoring And Dose Assessment For People Exposed To Ionising Radiation Following A Malevolent Act

Radiological and Nuclear Emergency Management: Aspects of Radiobiology

ENEA Casaccia Research Centre, Rome

6 November 2012

george.etherington@hpa.org.uk