The Threat of Chemical Weapons

1. The Threat ofChemical Weapons

2. Tokyo 1995 - Aum Shinrikyo • 27 June 1994 – Aum Shinrikyo sect released sarin in the central Japanese city of Matsumoto in response to a court case. Killed 7 and harmed 200. Role of Aum Shinrikyo not recognised at the time. • 20 March 1995 - Aum members released sarin in a co-ordinated attack on five trains in the Tokyo subway system, killing 12 commuters, seriously injuring 54, and affecting 980 more. More than 5000 presented themselves to hospital during the day. • 5 May 1995 - burning paper bag discovered in a toilet in Shinjuku station in Tokyo, the busiest station in the world. Revealed to be a hydrogen cyanide device “which, had it not been extinguished in time, would have released enough gas into the ventilation system to kill 20,000 commuters”.

3. Sarin in Tokyo • ~ 1L Sarin placed in plastic bags on floor of trains. Punctured with sharpened umbrella tips before Aum people walked off train. • However, volatility of sarin is low and very little was aerosolised. Shoko Asahara

4. 3 2 5 1 1 2 5 3 1 4 4

5. Sarin in Tokyo • ~ 1L Sarin placed in plastic bags on floor of trains. Punctured with sharpened umbrella tips before Aum people walked off train. • However, volatility of sarin is low and very little was aerosolised. • Only 4 deaths with 4 of the attacks despite hundreds of people being exposed. 2 of the deaths occurred in cleaners removing bags. • In 5th attack, a passenger identified the cause of the noxious substance and kicked it out of the door onto a crowded platform. ? aerosolised or contacted skin; 4 people died on platform. Shoko Asahara

6. Chemical weapon attacks on civilians • In 1995, the world was poorly prepared for chemical weapon attacks on civilian populations. This was despite the 1988 attack on the Iraqi kurdish village of Halabja which killed ~5,000 of the town’s 50,000 civilian population. • The trains in Tokyo were attacked over about 30 mins. Some of the contaminated trains kept running for hours, further affecting commuters. • It took hours for the fact that it was a chemical attack to be recognised and then even longer to recognise the causative agent. • Hopefully, we are much better prepared in the UK today . . .

7. Edinburgh - one lovely summer’s night • 03.00 in A&E. Late shift has just gone home. Pretty quiet. • Red phone goes off. Incident in a disco in town – small explosion, some smoke. Scores of people down quickly. Maybe 60, 70 people. • Paramedics have arrived on scene but people are already heading to hospital in private vehicles. They should be with you soon. • Hmmmmmm…… • Do we know what to do, or what chemical it might be, if this has been a chemical attack?

8. The first car arrives outside … • Three people apparently unconscious. One very agitated sweaty driver. Other cars approaching. • Should the injured come into A&E or be treated outside . . . . . ? • You start running through in your head all that you know about chemical weapons ……

9. Current major CW threat agents Blistering Agents (vesicants) Sulphur mustard* Nitrogen mustard Lewisite (also Mustard/Lewisite Mixture) Nerve Agents G agents :GB (sarin)*, GD (soman)*, GF V agents : VX*, R-33 (Russian V agent) GA (tabun)* (developing nations) Lethal Industrial Gases Phosgene Hydrogen Cyanide ?* Riot control chemicals (CS) New agents Globally, sulphur mustard and GB are the greatest threat

10. LCt50 (est) LD50 percutaneously mg.min m-3 (mg per 70 kg man) VX 10-30 * 5-10 GD 50-70 350 GB 100 1700 GA 135-400 1000 Lewisite 1 1200-1500 ~3500 Sulphur mustard 1500 (>~100**) 4500 (>~0.1**) Phosgene 3000 N/A HCN 5000 N/A The toxic hazard will be dependent on the volatility (for inhalation) and persistency (for skin) of the agent (* when aerosolised) (** effective doses) Toxicities by inhalation and skin contact

11. Dissemination As shown in Tokyo, the full effectiveness of chemical weapons can only be realized if they are dispersed so that they are delivered to individual people One can achieve this by breaking the bulk agent into vapour [for inhalation], tiny particles/aerosols or liquid droplets [skin & mucosal contact], or in rare cases powder [inhalation] One good method for dispersing chemical weapons is through combining them with explosives. Therefore, chemical injuries are likely to be combined with injuries from explosives. Adding a thickener to liquids increases persistence, adhesiveness and difficulty of decontamination

12. Volatility of CW agents B.Pt. (oC) Volatility at 25oC (mg per m3) Phosgene 8 >1,000,000 (Non-Persistent) Water 100 ~150,000 GB (sarin) 158 22,000 Lewisite 196 3900 GD (soman) 198 3900 Sulphur mustard 217 910 (Intermediate) GF 239 680 GA 247 490 Nitrogen mustard 257 110 VX 300 9 (Persistent)

13. Approach to diagnosis • Could this be cyanide? Rapid onset of symptoms after inhalational exposure Circulatory collapse, seizures, respiratory arrest Normal secretions, pupils. No fasciculation ** High lactate >10 mmol/L **

14. Hydrogen cyanide – chemical asphyxiant • Colorless, highly flammable gas or highly volatile bluish-white liquid. Odor of almonds but some cannot smell it. Gas lighter than air, so disperses quickly. • Inhibits cytochrome oxidase. • High [-CN] = immediate tachypnoea, gasping, then seizures, cardiovascular collapse. More moderate [-CN] = dizziness, headache, agitation, confusion. Coma, seizures if prolonged. • Rapid decontamination of liquid CN essential. • High flow oxygen, supportive care; measure blood lactate. • Specific antidote: dicobalt edetate or Na nitrite + thiosulphate. Not required if the patient is breathing normally and fully conscious five minutes after removal from source. Cyanide unlikely if lactate normal.

15. Approach to diagnosis • Could this be cyanide? • Could this be an organophosphorus nerve agent? Rapid onset of symptoms after inhalational exposure Collapse, seizures, respiratory difficulty & arrest Excessive secretions & sweat, miosis. Maybe fasciculations. But slower onset after skin exposure (eg VX) Localised fasciculations at site of skin exposure

16. Organophosphorus nerve agents • Colorless to brown fluids at room temp. Some have fruity odour. Variable volatility –> spray and aerosol. Vapours heavier than air. • Highly toxic; inhibit acetylcholinesterase. Single drop on skin can kill. • Cause cholinergic syndrome – respiratory failure (loss of central drive, NMJ dysfunction, direct lung effects), cardiovascular shock, seizures. Sweat, secretions, miosis, fasciculations. Poor vision. • Rapid decontamination of liquid nerve agent essential. High flow oxygen, suction, airway support/intubation. • Urgent use of specific antidotes: atropine (antimuscarinic), pralidoxime (AChE reactivator), diazepam. • **Beware nosocomial contamination**

17. Antidotes for OP nerve agents • Atropine 1-3 mg bolus, repeated every 5-10 min (possibly in doubling doses) to improve cardio-respiratory function • Pralidoxime 30 mg/kg over 30 min, then infusion of 8 mg/kg/min [Adult = 2g loading dose, then 0.5 g/hr] • Diazepam 10 mg bolus for agitation • It is essential that pralidoxime is given early, before ‘ageing’ has occurred. Combipen allows pre- hospital antidote administration.

18. Approach to diagnosis • Could this be cyanide? • Could this be an organophosphorus nerve agent? • Could this be Lewisite? Rapid onset of burns and blistering within minutes of exposure Blepharospasm, tearing eyes Cough, burning throat pain

19. Lewisite – vesicant/irritant • Arsenical compound - chlorovinyl dichloroarsine • Colorless and odorless. However, impurities are yellow or brown liquid with a distinctive odor (~geraniums). Heavier than air. • Affects skin, eyes, respiratory system (+/- systemic arsenical effects) • Rapid absorption through clothes and skin, and after inhalation • Immediate clinical effects. Severity increases with dose, exposure time, hot humid conditions. Liquid worse than gas. • Rapid decontamination essential. Specific antidote: BAL dimercaprol

20. Approach to diagnosis • Could this be cyanide? • Could this be an organophosphorus nerve agent? • Could this be Lewisite? • Could this be mustard? Burns and blistering, tearing eyes, cough and throat pain usually begin 2-12 hrs after exposure

21. Sulphur mustard – vesicant • Sulphur compound - 1,5-dichloro-3-thiapentane. First used 1917 • Colorless and odorless. However, impurities are yellow/brown liquid with a distinctive odor (~mustard/horseradish). Heavier than air. • Affects skin, eyes, respiratory system, (bone marrow) • Rapid absorption through clothes and skin, and after inhalation • Although tissue damage starts immediately, clinical effects are usually delayed. Latent period 1-24 hrs; then evolve over hrs/days. Severity increases with dose, exposure time, hot humid conditions. • Rapid decontamination essential. No antidote. Mortality 3-4% - aim is to incapacitate

22. Clinical effects of sulphur mustard

23. Approach to diagnosis • Could this be cyanide? • Could this be an organophosphorus nerve agent? • Could this be Lewisite? • Could this be mustard? • Could this be phosgene? Immediate onset of eye and skin irritation Rapid or delayed respiratory symptoms (dyspnoea, laryngospasm) Nausea, chest pain, hypotension

24. Phosgene – lung irritant • Colorless gas or white cloud at room temp. First used WWI 1915. May smell of musty hay/mown grass. Difficult to detect. • Heavier than air. Degrades slowly. • Not highly water soluble so reaches alveoli. Reacts with tissue water to produce hydrochloric acid • Immediate irritant effect – watering eyes, blepharospasm, N&V, wheeze, chest pain, haemolysis. Rarely early death. • After 2-72 hr latent period, patients develop pulm’ oedema, shock, ARDS. Can be precipitated by exercise. Outcome not predicted by dose/initial SxSx • Rx - High flow oxygen, bronchodilators, supportive care. Decontaminate. No specific antidote

25. Approach to diagnosis (HPA) • Could this be cyanide? • Could this be an organophosphorus nerve agent? • Could this be Lewisite? • Could this be mustard? • Could this be phosgene? • Could this be chlorine or another irritant gas? Immediate onset of eye and skin irritation Rapid onset of choking, coughing, wheeze

26. Chlorine – lung irritant • Green-yellow gas or clear amber fluid. First used WWI 1915. Smells of bleach/swimming pools. Highly reactive, explosive. Easily detected. • Heavier than air. Degrades slowly. • Highly water soluble - most effects in upper airway. Alveolar effects less common. With tissue water, produces hydrochloric & hypochlorous acids • Immediate upper airway irritant effect – coughing, choking, wheeze, dyspnoea, N&V. With large exposures, acidosis. Chemical pneumonitis, pulmonary oedema, ARDS may be delayed. • Stinging eyes, blepharospasm, erythema. Frostbite after contact with compressed liquid gas. • Rx - High flow oxygen, bronchodilators, supportive care. Decontaminate. No specific antidote

27. Organophosphorus pesticides as weapons • Important but little discussed. Freely available and cheap to buy • Toxic - 3500 mg of methyl parathion might kill a 70 kg adult by dermal exposure, cf 1700 mg for sarin. Very low volatility: chlorpyrifos 3 mPa Low risk of nosocomial contamination or explosive dispersion Smelly but this is likely due to solvents coformulants Solvents much more volatile: toluene 3 kPa (6 log difference) • Likely weapon use would be via contaminated water or food, as occurs throughout south Asia on a regular basis. • Contaminated flour in bread - hundreds of patients with no links appearing at multiple hospitals

28. Threat of chemical weapons • ?Not likely but, if a chemical weapon is used, things will move fast. You and the department will need to be up to speed. • The scenario was very loosely based on a CS explosion that occurred in a UK disco, bringing many people to A&E • Immediate chemical problems are cyanide and the nerve agents. Patients will die within minutes. Patients who make it to hospital are likely to be survivors or the worried well. • Mustard and Lewisite will kill few people but cause major chaos and overload medical facilities • Chlorine [and phosgene] are unlikely to kill many people but they will again cause chaos.