Chemical Weapons Syndromes - A Review-

1. Chemical Weapons Syndromes -A Review- John W. Faught, MAJ, MC Fort Benning, GA

2. Chemical Mass Casualty Events • Case study of a chemical terrorism event • History • Overview of chemical agents

3. Chemical Agent: Definition “A chemical substance…intended for use in military operations to kill, seriously injure, or incapacitate humans (or animals) through its toxicological effects.”

4. Case StudyThe Tokyo Subway Incident • Aum Shinrikyo cult • Possessed chemical, biological and possibly nuclear weapons • Rush hour on 3/20/95 released 11 one liter containers of liquid sarin in 5 locations on the Tokyo subway system • Well planned and executed attack in an ideal location • Delivery system: Perforating bags • 5510 casualties were reported including 12 dead (1000 chemical casualties)

5. The Tokyo Subway IncidentHospital Response • St. Luke’s International Hospital • Due to the earthquake risk in Japan this hospital holds regular disaster drills • 641 casualties were received in a short time • 5 critically ill • 106 with mild to moderate injuries • 530 mild • 2 eventually died

6. The Tokyo Subway IncidentKey Points • The incident was quickly recognized • Disaster plan was in place • No attempt was made to decontaminate the patients before they entered the hospital. Subsequently 20% of the hospital staff became symptomatic • Moderately well prepared hospital can save most patients. • Even under ideal conditions most nerve gas victims may be only mildly to moderately affected

7. Conclusions • Threat of a chemical mass casualty event is real • Identification of treatable agents is crucial • Medicine involved is straight forward. • Mass casualty plan should include decon • Primary Care medicine has an important role to play

8. History • Isolated use of cyanide known since ancient Greece • 1899 Hague Convention bans chemical warfare • 1914 WWI begins - Augustand quickly degenerates into a stalemate • Both sides explore options to break stalemate • Professor Fritz Haber suggests chlorine

9. History- 22 April 1915 • Chlorine gas used by Germany at Ypres, Belgium against the French and Canadians • 6,000 cylinders (168 tons) along a 7,000 m front • Both sides unprepared • Reported 5,000 casualties

10. History • Dec 1915 Phosgene gas by Germany at Ypres, Belgium against the British • May 1916 Diphosgene by Germany • decomposes to phosgene + chloroform • chloroform attacks mask filters • 1916 also saw the first use of Mustard gas • 1917 Cyanide gas used by France

11. WW I Chemical Casualties • 1.5 million deaths attributed to chemical attack in the first world war • Most gas casualties were due to Mustard gas • Chlorine and Phosgene produced 80% of the fatalities from chemical agent exposure in WW I

12. Between the World Wars • Italy against Ethiopia • Japan against China • Nerve gas synthesized in Germany in the 1930’s

13. World War II • Chemical weapons were available to all major countries • None were used, other than in China, due to fear of retaliation • Germany used cyanide gas Zyklon B in concentration camps

14. Post World War II • Egypt against Yemen- Mustard gas • Iraq against Iran, Kurds- Mustard and nerve gas • Apparent use in Syria- Cyanide

15. Classification of “Official” Chemical Agents • TOXIC AGENTS • those producing injury or death • INCAPACITATING AGENTS • produce temporary effects

16. “Official” Chemical Agents: Toxic Agents • Nerve agents (anticholinesterases) GA, GB, GD, GF, VX • Lung-damaging agents (choking agents) Chlorine, phosgene, [smokes] [vesicants] • Blister agents (vesicants) Mustard, Lewisite, Arsenicals • “Blood” agents (cyanogens)

17. Comparative Toxicity of CW Agents Ct50 (mg-min/m3) AGENT (L) (L) (L) (L) (L) (L) (E) (E)

18. Nerve Agents

19. Nerve Agents • GA (Tabun) • GB (Sarin) • GD (Soman) • GF • VX

20. Nerve Agents- Physical Properties • Clear, colorless liquids (when fresh), not “nerve gas” • Tasteless, most are odorless • Freeze/melt <0º C • Boil >150º C • Volatility GB>GD>GA>GF>VX • Penetrate skin, clothing

21. Nerve Agents- Toxicity ` LCt50 LD50 mg-min/m3 mg/70kg GA 400 1,000 GB 100 1,700 GD 70 50 GF 50 30 VX 10 10

22. Nerve Transmission: Nerve to Nerve ACh

23. Nerve Transmission: Nerve to Nerve ACh

24. Nerve Transmission: Nerve to Nerve ACh

25. Impulse Termination: The Role of AChE AChE ACh

26. Exposure to Nerve Agent AChE ACh

27. AChE ACh Exposure to Nerve Agent

28. ACh ACh ACh Receptors Nicotinic Nicotinic Preganglionicsynapses in ANS Skeletal muscle ACh Muscarinic Muscarinic Synapses in CNS Smooth muscle Exocrine glands ACh

29. Nerve Agent Effects • Vapor Exposure • Direct Exposure

30. Nerve Agent Effects- Vapors • Eyes: Miosis, injection, dim, blurred vision, pain • Nose: Rhinorrhea – “leaky faucet” • Mouth: Salivation, drooling • GI: Nausea, vomiting, pain, diarrhea • Respiratory: Severe breathing difficulty, gasping, irregular breathing compounded by excessive secretions

31. Nerve Agent Effects- Vapors Large exposure Previously listed effects plus... • Loss of consciousness • Seizures • Apnea • Flaccid paralysis • Death

32. Nerve Agent Effects- Direct Exposure • Small to moderate exposures- • Local- Blanching, localized sweating, localized fasciculations • GI symptoms will follow • Large exposures- • Symptoms are the same as after vapor exposure

33. Nerve Agent Effects- Cardiac • Muscarinic (vagal) decrease • Fright, Hypoxia and Nicotinic (ganglionic) increase • Heart rate may be high, low or normal • Hypertension

34. Nerve Agent Effects- CNS • Low Dose Exposures- • Slowness in thinking and decision making • Sleep disturbances • Poor concentration • Emotional problems • Larger Exposures- • Loss of consciousness • Seizures • Apnea and Death

35. Nerve Agent- Decontamination • MOST IMPORTANT! • Prevents further injury to the patient • Protects medical staff • Protective gear • Decontaminate casualty • Protects Hospital • Decontaminate casualty

36. Nerve Agent- Management- Antidotes • Too much acetylcholine • Block excess acetylcholine • AChE enzyme inhibited • Reactivate enzyme

37. Nerve Agent- Management- Atropine • An anticholinergic • Blocks excess acetylcholine • Clinical effects at muscarinic sites • Dries secretions • Reduces smooth muscle constriction • Not for skeletal muscle effects • Given systemically it will not treat miosis

38. Nerve Agent-Management- Atropine • Side effects in unexposed • Starting dose 2 mg to 6 mg • Repeat with 2 mg every 5 to 10 minutes until • Secretions drying • Ventilation improved • Usual dose: (severe casualty) 15 to 20 mg • Pediatric: 0.5mg between 15-40 lb; 1mg 40-90 lb

39. Nerve Agent- Management- Oximes • Pralidoxime Chloride (2-PAM Cl) most used in US • Remove agent from enzyme, unless aging has occurred • Effects at nicotinic sites • Increase skeletal muscle strength • No clinical effects at muscarinic sites

40. Nerve Agent- Management- Diazepam • Anticonvulsant, used to decrease brain damage due to prolonged seizures • In animal models this has been shown to improve outcome following superlethal doses of soman • Should be given to all seriously injured patients • Dose = 10mg

41. Nerve Agents- Recovery • Depends on specific agent • Without complications may be conscious, breathing, in 3 to 4 hours • With persistent agents or complications may require days to weeks of mechanical ventilation • Long term- unknown

42. Pulmonary Agents

43. Lung-Damaging Agents • Chlorine • Chloropicrin • Phosgene • Diphosgene • Distributed as aerosols or as gases/ vapors

44. Chemical-agent Damage to Respiratory System • Central effects predominate • Mustard • Lewisite • Chlorine • Peripheral effects predominate • Phosgene

45. Pulmonary Agents- Clinical Considerations • These agents cause pulmonary edema • Damage alveolar-capillary membrane • Latent Period • Symptom onset may be delayed hours to days • Objective signs appear later than symptoms • Sudden Death may occur • Laryngeal obstruction (edema/spasm) • Bronchospasm

46. Pulmonary Agents- Clinical Considerations • Infectious Bronchitis / Pneumonitis common • usually occurs 3-5 days post-exposure • fever, elevated WBC, infiltrates- not always infection • prophylactic antibiotics not indicated • Effects exacerbated by exertion • compensatory mechanisms overwhelmed • strict rest, even if asymptomatic • No specific therapy exists

47. Phosgene- CXR 7hrs 2hrs

48. Pulmonary agents - Therapy • Supportive care only • oxygen • positive pressure ventilation • Judicious use of PEEP • bronchodilators • Bacterial superinfection common (3-5 days out) • follow serial cultures • prophylactic antibiotics not indicated • No long-term sequelae (uncomplicated cases)

49. Blister AgentsVesicants

50. Vesicants- Mustard • Alkylating agent • Oily liquid • Light yellow to brown • Vapor heavier than air • Liquid heavier than water • Low volatility; persistent • Freezes/melts at 58°F