Assessment of biodosimetry methods for a mass-casualty radiological incident: medical response and management considerations

Abstract

Following a mass-casualty nuclear disaster, effective medical triage has the potential to save tens of thousands of lives. In order to best use the available scarce resources, there is an urgent need for biodosimetry tools to determine an individual's radiation dose. Initial triage for radiation exposure will include location during the incident, symptoms, and physical examination. Stepwise triage will include point of care assessment of less than or greater than 2 Gy, followed by secondary assessment, possibly with high throughput screening, to further define an individual's dose. Given the multisystem nature of radiation injury, it is unlikely that any single biodosimetry assay can be used as a standalone tool to meet the surge in capacity with the timeliness and accuracy needed. As part of the national preparedness and planning for a nuclear or radiological incident, the authors reviewed the primary literature to determine the capabilities and limitations of a number of biodosimetry assays currently available or under development for use in the initial and secondary triage of patients. Understanding the requirements from a response standpoint and the capability and logistics for the various assays will help inform future biodosimetry technology development and acquisition. Factors considered include: type of sample required, dose detection limit, time interval when the assay is feasible biologically, time for sample preparation and analysis, ease of use, logistical requirements, potential throughput, point-of-care capability, and the ability to support patient diagnosis and treatment within a therapeutically relevant time point.

Fig.1. Dose range in which the indicated assays are able to estimate absorbed radiation dose

The dotted line represents conflicting dose estimate reports for the LDK assay which indicate the range begins at either 0.5 or 1 Gy. For the gamma-H2AX method; the black column represents the dose range for the microscopy method, and the white column is representative of the dose range for the flow cytometry method of measurement.

Fig. 2. Time phased comparison of currently available dosimetry methods out to one week after detonation

Dotted lines represent time needed for sample preparation to occur before any results become available. Note: Some lymphocyte based assays recommend 12hours before drawing blood to allow lymphocyte circulation from tissues. For the gamma-H2AX method; the black bar represents the microscopy method, and the white bar is representative of the flow cytometry method of measurement. For PCC; the black bar represents the CHO method and the white bar represents the chemical stimulation method.

Fig 3. Biodosimetry model for using Point of Care and High Throughput Screening Systems for medical triage after an IND detonation

After the event it is anticipated that one million people could require biodosimetry screening to determine their dose of exposure to radiation. A point of care device with the use profile shown in Table 2 is preferred for the initial triage. After the first round of biodosimetry, it is anticipated that the number of people requiring additional testing will be reduced to around 400,000. More complex methods can then be used on this smaller population to refine initial dose estimates, with a high-throughput system being preferred.

Fig. 4. Stepwise triage process for use after an IND detonation

T- triage, DX – differential diagnosis, MD- medical doctor; triage categories are per Coleman et al. (2011) The time from time 0 until “normal” standards of care are in force will vary on distance from the incident.