The Threat ofChemical Weapons

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”.

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

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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

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 . . .

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?

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 ……

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

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

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

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)

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 **

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.

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

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**

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.

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

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

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

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

Clinical effects of sulphur mustard

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 irritationRapid or delayed respiratory symptoms (dyspnoea, laryngospasm)Nausea, chest pain, hypotension

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

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

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

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

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.