1. Chemical terrorism: Diagnosis and treatment of exposure to chemical weapons
By Dr HP Shum
ICU

2. History
The first modern use of chemical warfare (CWF) was on April 22, 1915 near Ypres, Belgium during WWI
Germans dispersed 150 tons of chlorine gas against French
generating 5000 pulmonary casualties among Allied troops
After the German chlorine gas attacks, Allied troops were supplied with masks of cotton pads soaked with urine because ammonia can neutralize chlorine or with NaHCO3
Soldiers found it difficult to fight like this
By July 1915 soldiers were given efficient gas masks and anti-asphyxiation respirators

3. History
Dr. Gerhard Schrader (25 Feb ) was a German chemist specializing in the discovery of new insecticides
He discover organophosphates which killed insects by interrupting their nervous systems
he accidentally discovered Tabun (1936) and subsequently also Sarin (1938), Soman (1944) and Cyclosarin (1949)
However, nerve gas was not used against Allied troops during WWII

4. History
During Iran-Iraq War ( ), Iraq used tabun against Iran, and Iran responded with a nerve agent of unidentified type
This exchange generated at least 10,000 deaths and casualties in the two armies

5. History
On March 16,1988, Iraq launched an attack on the Kurd population of Halabja, Iraq where there were 5000 deaths and a high number of casualties from both sarin and from sulfur mustard

6. History
A 1995 Tokyo subway attack by the religious cult Aum Shinrykio utilized sarin and caused 12 deaths and 5,000 casualties
In fact, one year earlier, the cult had conducted a test attack on an apartment building in Japan and killed seven people

7. Type of chemical agents
Nerve agents
Toxic asphyxiants
Pulmonary irritants
Blistering agents
Irritant agents (riot control)

8. Nerve Agents – introductions
prototypical nerve agent is sarin (沙林)
VX, soman (梭曼) and tabun (塔崩) are another examples
organophosphate esters
Mostly colorless, odorless, and tasteless, some with fruity smell
do not irritate the skin
hazardous in liquid, vapor, and aerosol forms
Exposure can occur via the lungs (fast, systemic), membrane of nose (fast, systemic), skin (slow, local), or eyes (slow, local)

9. inhibition of cholinesterase, which produces a state of acetylcholine excess

10. Nerve Agents - symptoms
Rapid onset of symptom and death occur in seconds to minutes
smooth muscle constriction (diarrhea, involuntary micturition), profuse secretions (lacrimation, running nose, sweating, salivation), small pupils and related visual disturbance (blurring of vision)
Skeletal muscle weakness with respiratory failure, circulatory collapse, convulsion, coma and death

11. Nerve Agents - symptoms
Large amouts of liquid agents on skin resulted in delayed symptoms
Commonly there is an asymptomatic period of 1 to 30 minutes, and then the sudden onset of an overwhelming cascade of events, including loss of consciousness, seizure activity, apnea, and muscular flaccidity

12. Nerve Agents – exposure
Leave the exposure area at once, and head to fresh air
do not lay down and do not remain in below-ground spaces
Cover the nose and mouth with a wet cloth if possible
Wear the gas mask immediately (within 9s), if you have any, after holding your breath
Seek treatment if any symptom occur

13. Nerve Agents - decontamination
Wear chemical protective overgarment, impermeable protective gloves, and overboots before contact with those exposed
Remove all clothing and all jewellery, placed into sealed double plastic bags
Shower immediately with soap and water, clean with eye with copious amount of water
Wash clothing with bleach

14. Nerve Agents - treatments
Atropine
2mg Iv/ Im
re-dosed at 2 mg IM every 5 to 10 minutes until muscarinic symptoms disappear
More than 200 mg of atropine may be required in the first 24 hours for nerve agent poisoning

15. Nerve Agents - treatments
Pralidoxime
cholinesterase reactivator
1 to 2 g IV within five minutes of presentation
Or 600mg IM
If weakness is not relieved or recurs after 20 to 60 minutes, the dose should be repeated

17. Nerve Agents - treatments
Supportive measures
Maintain a patent airway
Ventilator assistance and supplementary oxygen as needed to treat respiratory failure (high airway pressure due to large amount of secretion in bronchi). If intubation is required, avoid using succinylcholine so as to prevent excess release of Ach
Treatment of cardiovascular shock
Diazepam to control seizure (very common), 5-10mg IV/ IM, repeat in 10-20min time if needed
Patients may had long-term neurological damage, mainly affecting short term memory and also personality changes

18. Toxic asphyxiant - introduction
Cyanide (anion CN- or hydrocyanic acid, HCN)
Also known as “blood agent”
Colorless liquid
Highly volatile with gas that smells like almonds
Multiple industrial uses including the fumigation of ships and buildings, electroplating, metal cleaning and as rodenticide
Arsine (arsenic trihydride) is another agent in this class

19. Toxic asphyxiant - mechanism
Liquid cyanide is readily absorbed from the GIT and eye
Absorption by skin is slow and usually without significant clinical effect
Inhalation is the most important and toxic route during terrorist scenario

20. Toxic asphyxiant - mechanism
Following absorption, cyanide is quickly and widely distributed to all organs and tissues of the body
Combine rapidly with iron in cytochrome a3 in mitochondria to inhibit this enzyme, thus preventing intracellular oxygen utilization
anaerobic metabolism, creating excess lactic acid and metabolic acidosis
Typically blood well oxygenated with pinkish coloration as those of CO poisoning

21. Toxic asphyxiant - mechanism
Cyanide is eliminated unchanged from the body in breath and sweat
Urine excretion as sodium thiocyanate and cyanocobalamin(vitamin B12)
Cyanide also has a high affinity for the ferric iron of methemoglobin, and one therapeutic strategy is inducing the formation of methemoglobin to which cyanide preferentially binds

22. Toxic asphyxiant - symptom
Rapid onset of action (seconds to minutes)
Cyanide
mild irritation of the eyes, nose, and airways
Flushing of skin because capillary blood is unable to deposit oxygen in the tissues
tachypnea., tachycardia and headache
nausea and vomiting, confusion, muscular weakness, seizure, respiratory failure and cardiac arrest
Arsine
Similar to cyanide
Haemolysis as well causing ARF

23. Toxic asphyxiant - exposure
Leave the exposure area at once, and move to fresh air
Cover your nose and mouth with a wet cloth
Emergency responders must wear gas masks with charcoal filters

24. Toxic asphyxiant - decontamination
Remove clothing, which should be double bagged and sealed in plastic
Shower with soap and water for about 15 minutes (including the eye)

25. Toxic asphyxiant - investigations
Cyanide level (Mild effects may be apparent at concentrations of mcg/ml, and concentrations of 2.5 mcg/ml and higher are associated with coma, convulsions and death)
Lactic acidosis
Oxygen content of venous blood abnormally high

26. Cyanide exposure - treatments
Mechanical ventilation for respiratory failure
Circulatory support with crystalloids and vasopressors
Correction of metabolic acidosis with IV sodium bicarbonate
Seizure control with benzodiazepine administration
If the patient is conscious, then antidotes are usually not required (death usually occurs in about eight minutes with significant exposures)

27. Cyanide exposure - treatments
Two steps approach
Methemoglobin-forming agents
Amyl nitrite or Na nitrite
MetHb even higher affinity for cyanide than does cytochrome a3, causes dissociation of bound cyanide from cytochrome a3 and frees the enzyme to help produce ATP again
Vasodilation with postural hypotension frequently occurs required fluid challenge
Overproduction of metHb may compromise oxygen-carrying capacity and nitrite is relatively contraindicated in smoke-inhalation victims
Provision of a sulfur donor
Na thiosulfate
conversion of cyanide to thiocyanate and eliminate in urine

28. Cyanide exposure - treatments
Amyl nitrite ampules
Inhalation of broken ampules 30s for each minute for 3 min., may need 5 ampules in total
Sodium nitrite
300 mg over to 15 minutes with careful monitoring of blood pressure. Half the dose (150 mg) may be repeated after 30 minutes
Sodium thiosulfate
12.5g slow IV, can be repeated in 30 minutes at one-half of the initial dosages

29. Cyanide exposure - treatments
Combination of IV Na nitrite and IV Na thiosulfate is the best tx for cyanide intoxication
Capable detoxify approx. 20 lethal dose of cyanide and effect even respiration stop
As long as the heart is still beating, the chances of recovery using this tx is very good

30. Cyanide exposure - treatments
However, many patients will recover even without specific antidotal treatment if vigorous general supportive care is emphasized
Lack of availability of antidotes is therefore not a reason to consider even apneic cyanide casualties expectant

31. Cyanide exposure - treatments
Cobalt EDTA
directly chelate cyanide to reduce its toxicity
initial dose of 300 mg IV over one minute. The dose may be repeated twice at five minute intervals
Potentially fatal adverse events include hypotension, vomiting, hypertension, and cardiac arrhythmias
clear superiority to the methemoglobin formers has not been demonstrated
Hydroxocobalamin
combining with cyanide to produce cyanocobalamin (vit B12) and excrete in urine
10 mL of a 40 percent solution IV (4g) over 20 minutes
No significant S/E but efficiency still required more investigations

32. Arsine exposure - treatments
no specific antidote for arsine
Treatment is supportive and directed at the hemolysis and renal failure
Exchange transfusion and diuresis has been recommended
Dialysis is not useful in removing arsine or arsine-Hb complex

33. Pulmonary irritant - introduction
Phosgene, chlorine and ammonia
common industrial use and may be used by terrorists
high pulmonary exposures, they can cause death within 10 minutes

34. Pulmonary irritant - symptoms
nose and throat irritation, cough, and chest pain
shortness of breath and signs of pulmonary edema
Signs of acute lung injury that are seen within four hours of the exposure predict a low likelihood of survival
If the casualty survives, resolution commences within 48 hours, and in the absence of complicating infection, there may be little or no residual damage
Ammonia also causes severe long-term damage to the surface structures of the eye, leading to opaque corneas and cataracts

35. Pulmonary irritant - exposure
Leave the exposure area at once, and move to fresh air
Pulmonary agents are heavier than air, so do not lie down in the toxic area and do not go below ground level
Cover your nose and mouth with a wet cloth
Keep eye closed

36. Pulmonary irritant - decontamination
Remove clothing
water shower, and in particular flush the eyes with water for about 10 minutes
Gas mask required on patient contact if not well decontaminated

37. Pulmonary irritant - treatment
CXR similar to ARDS
Mechanical ventilation for pulmonary failure
Bronchospasm is treated with bronchodilators and steroid
Eyes should be treated with a mydriatic followed by a topical antibiotic
Treat secondary pulmonary infection accordingly
Absolute rest must be continued until the acute symptoms have disappeared

38. Blister agents - introduction
Prototype is sulfur mustard (硫芥氣)
brown oily liquid at room temperature that converts to a gas with weapon system delivery
Smell like garlic or onion
Toxicity to the eyes, skin, and lungs occurs via direct contact
Lewisite (路易氏劑) is another agent in this class
severity of a blister agent burn is directly related to the concentration of the agent and the duration of contact with the skin

39. Blister agents - mechanism
interference with DNA synthesis and with cell division
alkylating agents are related component in medical use eg cyclophosphamide
Thickened blister agents will contaminate terrain, ships, aircraft, vehicles, or equipment and present a persistent hazard

40. Blister agents - symptom
Respiratory system
Early respiratory symptoms are sore throat, cough, and hoarseness
Shortness of breath ensues in about 12 hours
Bacterial pneumonia on D3-4

41. Blister agents - symptom
Skin
Redness, pain and itchiness
Blisters form by 16 hours, max D3
Deep burns of the skin with slow healing and scarring may occur depending upon the level of exposure to the agent

42. Blister agents - symptom
Eye
symptom free for the first 12 hours
eye pain, and eyelid swelling
Blindness is uncommon, but damage to the ocular surface and cornea can be chronic and progressive
With Lewisite exposure, skin and eye symptoms begin immediately
Overall, the blister agents are designed to incapacitate victims rather than kill them. The mortality rate is usually about 4 percent but depends upon the dose received and the baseline health status of the victim

43. Blister agents - exposure
Leave the exposure area at once
Cover your nose and mouth with a wet cloth
Close your eyes as you escape
Blister agents are heavier than air, so do not lie down and do not go below ground level

44. Blister agents - decontamination
Clothing should be removed carefully so as to avoid exposing the skin to any residues on the material
Copious amount of water shower
0.5% Na hypochlorite for skin and hair
Flush the eyes with water for 15 minutes

45. Blister agents - treatment
No specific tx for sulfur mustard
Supportive treatment for extensive skin burns, pulmonary failure, eye damage, and later systemic effects such as infection and bone marrow suppression
Dimercaprol can be used as topical antidote of Lewisite. However, these dimercaprol products are difficult to obtain

46. Irritant agents - introduction
Local irritant causing eye, upper respiratory tract and skin irritation
dispersed as fine particulate smoke (aerosols) or in solutions as droplet aerosols
Examples of irritant agents are O-chlorobenzylidene malononitrile (CS), chloroacetophenone (CN)
used primarily in training and in riot control

47. Irritant agents - symptom
marked burning pain in the eyes with copious lacrimation, thin mucous nasal discharge, coughing, and dyspnea
heavy exposures result in nausea and vomiting
Exposure to extremely high concentrations in an enclosed space may cause tracheitis and bronchitis but permanent damage is very unlikely
Skin exposure causing irritant dermatitis with erythema and, rarely, blisters formation
Incapacitation begins in 20 to 60 seconds and effects last for 5 to 10 minutes after removal to fresh air

48. Irritant agents - exposure
Move out of the contaminated environment, keep eye open as much as possible
DO NOT rub the eyes

49. Irritant agents - treatment
Eye and wound clean with NS / water
Unbroken skin clean with water and soap
ophthalmic corticosteroid ointment may be used for more severe eye exposure, seek ophthalmological care
erythema and stinging sensation are transient and do not require treatment, topical steroid for delayed erythema
Rarely, severe pulmonary exposure can be treated as pulmonary irritant exposure

50. Pepper Spray Riot control or personal defense
active ingredient is capsaicin derived from fruits of plant in Capsicum genus including chillis
Many different grade with variable effect, some can burn skin just on contact
causing inflammation in the mucous membranes of the eyes, nose, throat, and lungs

51. Pepper spray
Temporary blindness occurs on contact with eyes along with intense burning
Loss of balance and muscle coordination may occur along with severe skin irritation and difficulty breathing
Psychological effects may include anxiety and panic
The length of the effects depend on the strength of the spray but the average full effect lasts around thirty to forty-five minutes

52. Pepper spray - treatment
No antidotes available
capsicum is not soluble in water but in fat
most effective solution is a combination of milk, honey, a mild detergent and a little baking soda
Victims should be encouraged to blink vigorously in order to encourage tearing, cooling with fan or take a cool shower

53. Useful websites Virtual Naval Hospital www.vnh.org
and
Chemical and biological weapons: implication for anesthesia and intensive care from British Journal of anesthesia 2002, 89 (2):

56. The End