1. Chemical Terrorism Amita Shroff, MD June 10, 2010

2. Chemical Terrorism - Background • Dates back many years • First use: World War I • Modern use of chemical terrorism • Cyanide: Chicago, Illinois – 1984 • Sarin :Tokyo, Japan-1995 • Carbamate Insecticide: Fresno, California – 1999 • Nicotine: Grand Rapids, Michigan – 2002

3. QUESTION 1 • Reports of an unknown Chemical Substance have been released during an outdoor family concert. Participants arrive to the ED with C/O copious oral/nasal secretions, labored breathing, and muscle fasciculation. What othre PE finding should you expect? • A. Dry Skin • B. Miosis • C. Normal Mental Status • D. Constipation • E. Hypotension

4. QUESTION 2 • Group of boy scouts present to ED. They were hiking and encountered an oily, dark brown liquid with a mustard odor. They had erythema and blisters of the leg. Some have eye irritation and SOB. Which would be helpful in treating these patients • A. Supportive care only • B. Atropine and 2-PAM • C. Sodium Nitrite • D. Midazolam • E. Ciprofloxacin

5. QUESTION 3 • Terrorist release a chemical in a school with an odor of newly mown hay. Few hrs later, students start complaining of ocular and nasal irritation followed by DIB and cough. Those seen in ED have CXR with pulmonary edema. Most likely chemical of use is: • A. Phosgene • B. Sarin • C. Cyanide • D. Lewisite • E.Mase

6. QUESTION 4 • A foreign diplomat’s 12 yr son presents to the ED with C/O headache and nausea. He soon develops severe dyspnea and cyanosis. As he is moved into the trauma bay, he starts to seize. You suspect he has been exposed to: • A. Soman • B. Cyanide • C. Sulfur Mustard • D. Phosgene • E. 1-Chloroacetophenone

7. QUESTION 5 • Terrorist have released a chemical in a school bus full of children across the street from the hospital. In preparation for decon, HOSPITAL PERSONNEL should don what type of PPE? • A. Self –containing breathing apparatus (SCBA), fully encapsulating chemical protective suit • B. SCBA, chemical resistant clothing • C. Full face air purifying respirator, chemical resistant clothing • D. Coveralls and safety shoes/boots • E. Gown and gloves

8. Chemical Terrorism - Background • Apocalyptic groups • Aum Shinrikyo, Japan (1995) • Restoration of the 10 Commandments, Uganda (2000) • Political groups • Hamas/Hizbollah, Middle East (2000-present) • Western Group of Federal Forces, Chechnya (2000) • Revolutionary Armed Forces of Colombia (2001) • Al Qa’ida (2001-present)

9. 1995: Nerve gas attack on Tokyo subway

10. 1995: Nerve gas attack on Tokyo subway • Aum Shinrikyo converge at Kasumigaseki subway station • Release lethal sarin gas • Terrorists take sarin antidote and escaped • Commuters, blinded and gasping for air, rushed to the exits • Twelve people died, over 5,000 were treated in hospitals (many comatose state) • Japanese police raided Aum Shinrikyo headquarters • Arrested hundreds of members, including: Master Shoko Asahara.

11. 1995: Nerve gas attack on Tokyo subway Master Shoko Asahara (Cult Leader)

12. Chemical Terrorism - Effects • Toxic effects: • Topical injury • Skin • Eyes • Mucous membranes of respiratory tract • Systemic absorption • Dermal • Respiratory

13. Chemical Terrorism - Treatment • General treatment of contaminated victims: • Triage • Emergent resuscitation • Decontamination if needed • Airway / cardiopulmonary support • Emergent antidotal therapy

14. Decontamination

15. Chemical Terrorism - Decontamination • Decontamination • Appropriate level PPE required (hot zone) • Field / Special designated area outside the ED • Simple disrobement: removes ≥ 80-90% • Irrigation with soap and tepid water • 0.5% sodium hypochlorite (adults) • Pediatrics Considerations: • Warmer water (>37.8C) • Low pressure systems

16. Chemical Terrorism - Decontamination • Vapor exposure: clothing removal and hair-washing (sufficient) • Liquid dermal exposure: thorough decontamination necessary • Ocular exposure: copious irrigation

17. Chemical Terrorism - PPE • Level A • Highest level of protection • Highly contaminated area (hot zone) • Self contained breathing apparatus (SCBA) • Fully encapsulated suit • Slightly pressurized • Chemical resistant gloves • Hot, bulky and clumsy

18. Chemical Terrorism - PPE • Level B • Lower level than A • Respiratory protection, less skin protection • Outside hot zone / partially decontaminated pts • SCBA • Non-pressurized suit • Butyl rubber gloves/boots • Hot, bulky and clumsy

19. Chemical Terrorism - PPE • Level C • Lower than Levels A & B • Contaminants have been identified (low [ ]) • Air-purifying respirator: sufficient • Some protection against skin contact • Equipment: easier to work with

20. Chemical Terrorism - Agents • Nerve agents • Vesicants • Pulmonary agents (irritant gases) • Riot control agents • Incapacitating agents • Cyanide

21. Nerve Agents • Highly toxic • Organophosphate insecticides (signs and symptoms) • Powerful inhibitors of acetylcholinesterase (AChE) • Acetylcholine accumulation → abnormal neurotransmission

22. Nerve Agents Breakdown of Acetylcholine Acetylcholine accumulation AchE inhibited by nerve agent →Acetylcholine accumulation → Abnl neurotransmission

23. Nerve Agents – Clinical Sx’s Cholinergic Syndrome

24. Nerve Agents – Clinical Sx’s Cholinergic Syndrome

25. Nerve Agents • Onset and type of symptoms depends: • Concentration • Route of exposure • Vital sign abnormalities: • Sympathetic ganglia • Parasympathetic ganglia

26. Nerve Agents - Exposure • Low doses: • Miosis • Cojunctival injection • Pain • Rhinorrhea • High doses: • Respiratory effects • Severe exposure: • Neurologic findings • Death: • Respiratory depression and apnea

27. Nerve Agents - Exposure • Vapor exposure (triad): • Ocular • Nasal • Respiratory • Dermal exposure (progression): • Localized sweating and fasciculations → nausea, vomiting , diarrhea and fatigue • Severe exposure → respiratory and neurologic symptoms

28. Nerve Agents • Children: • Less likely: miosis and peripheral parasympathetic effects • More likely: CNS depression, hypotonia, weakness and seizures • Animal studies: children only need 10-33% of lethal dose on an equivalent mg/kg basis

29. Nerve Agents - Examples 1995: Sarin episode in Tokyo

30. Nerve Agents - Management • Self protection / PPE (contamination HIGH) • Agents readily absorbed • Patient decontamination: • Warm water / soap • ? Diluted bleach solution (adults)

31. Nerve Agents - Management • Restoring ventilation and oxygenation • Aggressive use of antidotes • Cardiac monitoring: dysrhythmias (torsades) • Benzodiazepines – neuroprotective • Close observation

32. Nerve Agents - Antidote • Atropine • .05 -.10 mg/kg IV or IM • Min 0.1mg, max 5mg • Repeat Q 2-5 min for secretions • Pralidoxime (2-PAM) • 25-50 mg/kg IV or IM • Max 1 gm • Repeat Q 30-60 min (persistent weakness)

33. Nerve Agents - Antidote

34. Nerve Agents - Antidote • Military Mark I autoinjector kits: • 2 mg of atropine • 600 mg of 2-PAM • Immediate IM use in the field • Stockpile (civilian first responder) • Not approved in pediatrics • Pediatric auto-injector recently approved

35. Nerve Agents - Aging • Aging: permanent inhibition of AChE activity (irreversible covalent binding) • Need early 2-PAM therapy prior to aging

36. Nerve Agents • Difference from organophosphate pesticide poisoning: • Continuous infusions usually not necessary (atropine or 2-PAM) • Delayed peripheral neuropathies not seen • Life support + antidotal therapy →prognosis good • Potential advances in treatment: • More effective oximes: HI-6 • Fetal bovine serum acetylcholinesterase

37. Vesicants • Vesicants: agents that produce blistering • Severe dermal manifestation in children • Released as an aerosol • 3 primary vesicants:

38. Vesicants - Sulfur Mustard (SM)

39. Vesicants - Sulfur Mustard (SM) • Most viable threat ( ≥ 12 countries have SM in their arsenals) • Easiest to synthesize • WWI: more casualties then all chemical agents combined • 1980’s: >45,000 casualties in Iran-Iraq war

40. Vesicants - Sulfur Mustard (SM) • Alkylating agent, highly reactive and electrophilic • Oily liquid with odor of garlic, mustard or horseradish • LD 50 is approximately 1.5 teaspoons • Clinical effects: dose dependent • Symptoms usually delayed for 4-8 hours

41. Vesicants - Sulfur Mustard (SM) • Symptoms: • Low doses: vessication • Higher doses: vessication and systemic toxicity • Skin: erythema → blister formation • Ocular: edema, conjunctival injection, corneal ulceration • Respiratory: cough/hoarseness, tachypnea, bronchospasm, pulmonary edema

42. Vesicants - Sulfur Mustard (SM) • Systemic absorption involves: • Hematopoietic • GI • CNS • Expected mortality = 3% for those reaching medical facility • Children: • More rapid onset • Worse dermal reactions

43. Vesicants – Lewisite (L)

44. Vesicants – Lewisite (L) • Potency similar to sulfur mustard • Oily, colorless liquid with geranium odor • Released by Japan during wartime • Known stockpiles in Russia • Active ingredient: trivalent arsenic • Inhibits various enzymes and glycolysis • Skin irritation and pain present within 15-30 minutes, blister formation by 2 hours

45. Vesicants – Lewisite (L) • Skin lesions: • less erythema • more tissue destruction then sulfur mustard lesions • Ocular pain and irritation within minutes • Central airway inflammation and upper airway irritation • Edema in severe cases • Hypotension and hemolytic anemia rare

46. Vesicants – Lewisite (L) • BAL (British anti-Lewisite) or dimercaprol: • Arsenic chelator • Prevents / decreases severity of skin and eye lesions if applied within minutes of exposure • Topical form not widely available • IM BAL reduces mortality from systemic effects of lewisite

47. Vesicants – Phosgene Oxime (CX) • Extensive tissue damage • Instantaneous pain and irritation of the skin, eye and airways • Skin → blanches → turns gray → urticarial, erythematous and edematous → necrosis / eschar formation • True vesicle formation DOES NOT occur

48. Vesicants – Phosgene Oxime (CX) • Ocular findings similar to lewisite • Pulmonary edema is common and may see bronchiolitis

49. Vesicants • Vesicant toxicity: clinical diagnosis • Urinary thiodiglycol metabolites will confirm sulfur mustard exposure • Death most frequently occurs 5-10 days after exposure (pulmonary insufficiency / infection) • Long-term hospitalization expected

50. Vesicants - Treatments • PPE for healthcare workers • Immediate decontamination (water and soap) • Only water for phosgene oxime exposure • Dilute hypochlorite solution (adults) – for water insoluble mustards and lewisites