Radiological Terrorism: Medical Response to Mass Casualties Part II

1. Radiological Terrorism:Medical Response to Mass CasualtiesPart II Jeffrey B. Nemhauser, MD Medical Officer Radiation Studies Branch National Center for Environmental Health Centers for Disease Control and Prevention

2. TriageKey Concepts • Victim categories following radiological/nuclear incident • (Possibly) exposed • Injured and Uninjured • Unexposed • Injured and Uninjured

3. TriageKey Concepts • Combined Injury • Physical, thermal, and/or chemical trauma • Radiation exposure in doses sufficient to threaten overall survival / recovery

4. TriageKey Concepts • Radiation Exposure (Irradiation) • High doses – combined with trauma – can cause serious or life-threatening illness • At very high doses, irradiation by itself may cause early, life-threatening adverse health effects

5. TriageKey Concepts • Triage during first 24 hours • Consider irradiation • Treatment decisions based on • Adverse Health Effects • First 24–48 hours • Laboratory Test Results • History (medical and exposure) • Contamination Assessment

6. Adverse Health EffectsAcute Radiation Syndrome (ARS) • ARS caused by irradiation of whole body or significant portion thereof • Adverse health effects • Type, severity, and time to onset dependent on radiation dose (i.e., amount of energy deposited in the body)

7. Adverse Health EffectsAcute Radiation Syndrome (ARS) • Three stages of ARS • Prodrome • Latent Period • Manifest Illness

8. Adverse Health Effects Acute Radiation Syndrome: Prodrome • Begins after exposure • Lasts 24–48 hours • Adverse health effects • Nausea/vomiting/diarrhea, fatigue, headache, parotitis, erythema, fever

9. Adverse Health Effects Acute Radiation Syndrome: Prodrome • Prodromal adverse health effects • Onset occurs more rapidly with severe ARS than with mild ARS • Nausea and vomiting are hallmark • Time to emesis may be used as rough estimate of exposure and outcome

10. Adverse Health Effects Acute Radiation Syndrome: Prodrome • Estimation of severity of ARS following a single acute dose exposure • Onset of vomiting within 1-2 hours is highly suggestive of a poor prognosis Source: Berger, et al. [2002]. Hospital Triage in the First 24 Hours After a Nuclear or Radiological Disaster. REAC/TS Training Site. http://www.orau.gov/reacts

11. Adverse Health Effects Acute Radiation Syndrome: Prodrome Source: Ann Intern Med [2004] 140(12):1037-1051. http://www.annals.org

12. Adverse Health EffectsAcute Radiation Syndrome: Prodrome Source: Ann Intern Med [2004] 140(12):1037-1051. http://www.annals.org

13. Laboratory TestingAcute Radiation Syndrome: Prodrome • Lymphocytes • Highly radiosensitive • Progressive decline in absolute lymphocyte counts provides early estimate of injury and outcome • Obtain baseline CBC with differential and repeat for 24–48 hrs. Absolute Lymphocyte Count Source: Andrews, et al. [1965] Personal Dosimetry for Radiation Accidents. Vienna: International Atomic Energy Agency.

14. TriageCombined Injury *Variability is dependent on the nature and extent of traumatic injury. Source: Adapted from Ann Intern Med. [2004] 140:1037-1051. http://www.annals.org

15. TriageWrap-Up • Acute Radiation Syndrome • 3 stages – Prodome is triage key • Clinical guides to victim triage • Time to prodrome onset (vomiting) • Total lymphocyte count • Combined injury generally means a worse prognosis

16. Radiological Terrorism Internal Contamination • Time-dependent phenomenon • Related to physical properties of isotope • Incorporation can occur rapidly

17. Radiological Terrorism Internal Contamination: Diagnosis • Exposure history • Potential for inhalation or ingestion • Open wounds containing shrapnel • Bioassay • Complete Blood Count • Urinalysis for radiation

18. Radiological Terrorism Internal Contamination: Treatment • Treatment most effective when administered early • Decision to treat may be based on preliminary data • Block or decorporate and treat effects of exposure

19. Radiological Terrorism Internal Contamination: Treatment • Anti-emetics as necessary • Ondansetron, granisetron, or other serotonin receptor antagonists • Anti-diarrheals • Loperamide hydrochloride, Lonox (diphenoxylate/atropine) • Replace fluids and electrolytes as necessary

20. PharmacotherapyPotassium Iodide • IOSAT™; ThyroSafe™; Thyro-Block™ • ThyroShield™ solution for children • Orally administered radioactive iodine blocking agent • Prevents radioactive iodine uptake in thyroid gland by competing for binding sites

21. PharmacotherapyPotassium Iodide • Radioactive iodine release scenarios • Nuclear power plant incident • Detonation of improvised nuclear device • “Dirty bomb” is unlikely source

22. PharmacotherapyPotassium Iodide • Blockade of radioactive iodine uptake is time-dependent • KI is 80% effective at 2 hours post-exposure; 40% effective at 8 hours Source: Health Physics [2000]. 78(6):660-7.

23. PharmacotherapyPotassium Iodide • Thyroid of fetus and young children more sensitive to carcinogenic effects of radioiodine • Radioiodine uptake inversely proportional to thyroid size

24. PharmacotherapyPotassium Iodide • Administration guidance available from US Food and Drug Administration (FDA) • Guidance based on prevention of thyroid cancer Source: Potassium Iodide as a Thyroid Blocking Agent in Radiation Emergencies [2001]. http://www.fda.gov/cder/guidance/4825fnl.pdf

25. PharmacotherapyPrussian Blue • Ferric (III) hexacyanoferrate (II) (Radiogardase®) • Orally administered decorporation agent (capsules) • Promotes fecal excretion of radioactive cesium and thallium

26. PharmacotherapyPrussian Blue • Binds isotopes in gastrointestinal tract via ion-exchange, adsorption, and mechanical trapping; limits entero-hepatic recirculation • Does not treat complications of radiation exposure • Need concomitant supportive care

27. PharmacotherapyPrussian Blue • Initiate treatment as soon as possible • Treat for minimum of 30 days • Duration based on level of contamination • Additional guidance • http://www.fda.gov/cder/drug/infopage/prussian_blue/default.htm • http://www.bt.cdc.gov/radiation/prussianblue.asp • http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202737.html • http://www.orau.gov/reacts/prussian.htm

28. PharmacotherapyDTPA • Diethylenetriaminepentaacetate • Calcium (Ca) and zinc (Zn) salts • Intravenous chelating agents for • Plutonium, Americium, Curium • DO NOT USE for • Uranium, Neptunium

29. PharmacotherapyDTPA • Ca-DTPA • Administration within 6 hours of exposure is most effective • Initially 10x more effective than Zn-DTPA • 24 hours post-exposure Ca-DTPA and Zn-DTPA have equivalent efficacy • Causes depletion of zinc and magnesium

30. PharmacotherapyDTPA • Ca-DTPA contraindications • Minors, pregnant women, serious kidney disease, bone marrow suppression • Check renal function prior to each administration

31. PharmacotherapyDTPA • Additional Guidance • http://www.fda.gov/cder/drug/infopage/dtpa/default.htm • http://www.orau.gov/reacts/calcium.htm • http://www.orau.gov/reacts/zinc.htm • http://www.bt.cdc.gov/radiation/dtpa.asp

32. PharmacotherapyFilgrastim (Neupogen®) • Colony Stimulating Factors (CSF) • Endogenous glycoproteins • Induce hematopoietic progenitor cells of bone marrow to proliferate and differentiate into specific mature blood cell types

33. PharmacotherapyFilgrastim (Neupogen®) • Filgrastim [Granulocyte-CSF (G-CSF)] • Genetically engineered protein • Daily IV or IM administration • Minimal effect on hematopoietic cell types other than neutrophil progenitors

34. PharmacotherapyFilgrastim (Neupogen®) • FDA-approved for treatment of neutropenia resulting from myelosuppressive cancer therapy • Not approved for treatment of ARS • Used as investigational drug for persons with unintentional radiological exposures

35. PharmacotherapyFilgrastim (Neupogen®) • Side effects • Allergic reactions (< 1 in 4000 patients) • Good response to antihistamines, steroids, bronchodilators and/or epinephrine • ~50% have recurrence on re-exposure • Fatal and non-fatal splenic rupture • Severe sickle cell crises in patients with sickle cell disease

36. PharmacotherapyFilgrastim (Neupogen®) • Additional Guidance • http://www.bt.cdc.gov/radiation/neupogenfacts.asp • http://www.accessdata.fda.gov/scripts/cder/onctools/labels.cfm?GN=Filgrastim

37. TreatmentWrap-Up • Pharmacotherapy must be administered quickly after exposure • Match the treatment to the exposure • Guidance is available from the FDA and CDC concerning appropriate administration