Chemical Agent Terrorism
by Frederick R. Sidell, M.D.
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Chemical Agent Terrorism
Frederick R. Sidell, M.D.
INTRODUCTION
On March 20, 1995, terrorism changed. For the first time, terrorists
used a chemical warfare agent against a civilian population. The nerve
agent sarin (GB) was released in the Tokyo subway system causing
over 5500 people to seek medical attention. Although terrorists had
released sarin previously outside an apartment building in the city of
Matsomoto in June 1994, this earlier use was felt to be directed at a
few people living in the building and not an attack on the general
population.
The Aum Shinrikyo cult is accused of both these attacks and also of
several other less successful efforts in the Tokyo subway system. This
cult, with a large membership and assets of over a billion dollars, had
a large facility for the manufacture of chemical warfare agents and of
biological agents. This organization has a following in several
European countries, including Germany and Russia, and in the United
States. Whether or not one believes that this cult will strike in this
country the point has been made: chemical warfare agents are now
terrorist weapons.
Chemical warfare agents can readily be synthesized by a skilled
chemist if the precursors are available. The processes for synthesis are
readily available and are even on the Internet. Although these has
been an international embargo on many of the precursors, this ban
does not apply to intracountry shipment.
Can terrorist groups in this country obtain or manufacture these
agents? One would like to think not, but this would be wishful
thinking. To date, the intelligence and law enforcement agencies have
been quite vigilant, and these agents have not been used. Any threat,
such as the threat of sarin use at Disneyland last Easter, is taken very
seriously.
How and where might such agents be used? Most chemical warfare
agents are liquids. They evaporate at different rates to produce vapor ;
cyanide is very volatile and the blister agent mustard and nerve agent
VX have a volatility similar to that of light motor oil. It is unlikely
that the liquid form would be effective in contaminating large
numbers of people. It would have to be spread over an area in places
that people will contact the droplets. To be effective liquid must be
dispersed. This can be done by aerosolizing it by an aerial spray (such
is done with pesticides) or by an explosion. Or the liquid agent can
be allowed to evaporate and the vapor dispersed by some means. In
the Tokyo the liquid sarin was placed on the floors of subway cars
and allowed to evaporate without dissemination, which is why there
were only 1000 casualties (most of whom had mild effects) out of the
5500 people who sought medical attention. Even a small fan would
have spread the vapor causing more casualties. When used outside a
vapor will not remain in place because even a small wind will dilute it
and carry it away. However, when dispersed inside there would be no
wind, and the agent vapor would remain and the concentration would
build, at least until the ventilation system removed it. On the other
hand, the ventilation system could well be the means of
dissemination.
The site of agent use would depend on the objectives of the user. For
maximal publicity one might chose a major event, such as the
Olympics (parts of which are held inside), the political conventions
(inside events), or even a major sporting event (most of which are
outside). For the maximal number of casualties a busy subway system
(an inside area) would be a good target. To make a statement and as a
warning of attacks to come, a site in a smaller community might be
the target. Terrorist attacks are unpredictable. Did anyone predict
bombings in the World Trade Center and Oklahoma City or a train
derailing in the southwest? We do not know where an attack might
be.
CHEMICAL WARFARE AGENTS
Nerve agents
Nerve agents are extremely potent organophosphorus compounds that
cause biological effects by inhibiting the enzyme
acetylcholinesterase. The more widely known nerve agents are tabun
(GA), sarin (GB), soman (GD), GF, and VX. They are similar in
structure and biological activity to some commonly used insecticides,
such as Malathion7, and are similar in biological activity to
carbamates used as insecticides, such as Sevin7, and used in
medicine, such as Mestinon7, Neostigmine7, and Antilirium7.
When the enzyme acetylcholinesterase is inhibited the
neurotransmitter acetylcholine accumulates to cause overstimulation
of those structures innervated by the cholinergic nervous system,
namely skeletal muscles, smooth muscles, exocrine glands, and
certain nerves both in the central nervous system and at ganglia. The
resulting effects, which are dependent on route and amount of
exposure, are shown in Table I.
Table I
Effects of Nerve Agents<br>
Eyes: Miosis, tearing, conjunctival injection (pain, dim vision, blurred vision)<br>
Nose: Rhinorrhea<br>
Airways: Bronchoconstriction, bronchosecretions (dyspnea, cough)<br>
Gastrointestinal: Hypermotility, secretions (nausea, vomiting, diarrhea, cramps)<br>
Skeletal muscles: Fasciculations, twitching, paralysis (weakness)<br>
Central nervous system: Immediate--loss of consciousness, seizures,<br>
apnea. Later--possible difficulty in thinking, impaired judgement, and other minor effects.<br>
Other: Salivation, sweating
Nerve agents are clear, colorless liquids with no perceivable odor
(although two are said to have a slight odor, this is not a reliable
detection method). The four "G-agents" are volatile to some degree,
but the most volatile, sarin, evaporates at about the rate that water
does. They all penetrate the skin and normal clothing well so
exposure might be by skin penetration or from vapor. Most exposures
to sarin have been from vapor.
All of these effects do not appear in every casualty; for example,
miosis is uncommon in someone exposed to a droplet of agent on the
skin unless the droplet is large enough to cause severe effects. After
exposure to a small amount of vapor, the triad of miosis, rhinorrhea,
and airway effects sometimes occurs, but often only one or two of
these effects occur.
The more common effects from each route of exposure are shown in
Tables II and III. The onset of effects from vapor is within seconds or
a minute of exposure, whereas the onset of effects from a liquid
droplet is from several minutes to 18 hours after contact. The rapidity
with which the droplet penetrates depends on the size of the droplet;
the larger the droplet the sooner the onset and the more severe the
effects.
Table II
Vapor exposure<br>
Mild:<br>
Miosis<br>
Rhinorrhea<br>
Dyspnea<br>
Nausea<br>
Weakness<br>
Severe:<br>
Above plus<br>
Loss of consciousness<br>
Seizures<br>
Apnea<br>
Onset:<br>
Seconds to minutes
Table III
Liquid exposure
Mild: Local sweating and fasciculations<br>
Moderate: Nausea, vomiting, diarrhea, weakness<br>
Severe:<br>
Above plus<br>
Loss of consciousness<br>
Seizures<br>
Apnea<br>
Onset: 5 min to 18 hours
Blood cholinesterase is generally inhibited, or depressed, after
exposure to a nerve agent, except that a small amount of vapor
affecting the eyes, nose, and airways may or may not be absorbed to
cause this inhibition. The erythrocyte (or red cell) cholinesterase is
more sensitive to nerve agent inhibition and measure of this--rather
than the plasma (or serum) enzyme--is preferred.
Antidotes for nerve agent poisoning are atropine and pralidoxime
chloride. Atropine blocks the effects of the excess acetylcholine at
muscarinic sites (drying secretions, reducing muscular contraction in
the airways and gastrointestinal tract), and pralidoxime chloride
removes the agent from the enzyme allowing the enzyme to once again
function (this drug is ineffective in soman poisoning). Clinically,
pralidoxime chloride reverses effects in organs with nicotinic receptor
sites (skeletal muscles).
Generally, in casualties with mild or moderate effects (Tables II and
III) 2 mg of atropine should be used initially and will usually be
sufficient. In a severe casualty, 6 mg of atropine (im) and 1 gram of
pralidoxime chloride (infused slowly over 20-30 minutes) should be
given initially. Miosis does not respond to the usual amounts of im or
iv atropine and should be treated with a topical preparation only if the
pain is severe. Atropine, 2 mg every 5-10 minutes, should be
continued until (a) secretions are drying and (b) ventilation is
adequate. Diazepam should be administered to every severe casualty
whether seizing or not, and ventilation and suction of the copious
secretions may also be necessary.
Vesicants
Vesicant agents are so named because they cause blisters. Sulfur
mustard is the most widely known of this class; others are Lewisite
and phosgene oxime. Nitrogen mustard (Mustargen7), used in cancer
chemotherapy for over 50 years, is a by-product of research on sulfur
mustard. In World War I, mustard caused large numbers of casualties,
but fewer than 5% of the casualties died.
In addition to causing blisters, mustard also damages the eyes and
airways by topical contact and the gastrointestinal tract and bone
marrow after absorption. Mustard evaporates at about the same rate as
thin motor oil, but despite this low volatility most battlefield
casualties have been from vapor.
Mustard crosses the skin or mucous membrane barrier and within a
minute or two after contact it attaches to cellular or tissue
components where it will later cause damage. Decontamination later
than a minute or two after contact will reduce but not prevent tissue
damage. Mustard causes no clinical effects (including pain) on
contact, and it is only hours later that the damage becomes apparent.
Sometime between 2 and 24 hours later (usually 4 to 8 hours) the
skin will redden, and this erythema will be followed by blister
formation sometime later. The initial effect in the eye is irritation and
reddening, and depending on the amount of exposure there may later
be inflammation and edema of the lids (to force the eyes closed
causing "blindness") and corneal damage. Airway damage, which
begins with destruction of the mucosa, starts in the nose and sinuses
and descends down the airways in a dose-dependent manner to
produce hoarseness and a non-productive cough. Once the agent is in
the lower airways, a productive cough is accompanied by increasing
dyspnea. In severe instances, the necrotic mucous membranes form
pseudomembranes.
Gastrointestinal disturbances are common in the first day after
mustard poisoning and are due to non-specific factors. Days later, if
the mustard was ingested or large amounts were absorbed, the mucosa
of the gut is destroyed leading to massive fluid loss. Mustard is
considered a radiomimetic agent because of this and other tissue
damage. When absorbed in large amounts mustard destroys the
precursor cells in the bone marrow leading to leukocytopenia; this is
followed by a decrease in red cells and platlets. Sepsis is not
uncommon in severe poisoning.
There is no antidote to mustard poisoning. Management consists of
keeping the skin lesions clean by frequent irrigation and application
of topical antibiotics, good pulmonary care including intubation and
assisted ventilation, and irrigation of the eyes followed by frequent
application of topical antibiotics. Fluid loss from mustard burns is
not of the magnitude seen after thermal burns, and one should resist
the temptation to overload with fluids.
Lewisite and phosgene oxime cause pain on contact with agent vapor
or with liquid agent. Because of this the casualty is more likely to
leave the area and decontaminate than he is after mustard poisoning in
which he has no sign of agent contact. Signs appear much earlier after
these two agents than after mustard exposure. Both cause skin, eye,
and airway damage, but neither causes bone marrow depression. The
antidote for Lewisite, British-Anti-Lewisite (BAL), is useful if
applied early.
Cyanide
A lethal amount of cyanide causes death within minutes, but lower
amounts produce few effects. There are two forms of cyanide, the
solid salts (sodium, potassium, and calcium) and the volatile liquids
(hydrogen cyanide and cyanogen chloride). The addition of an acid,
such as sulfuric acid, to a salt produces the vapor or gas of cyanide.
This was used in executions (the "gas chamber"), and these
components were found unmixed in Tokyo subways. Large amounts
of cyanide are required to cause death, compared to the amounts
needed for nerve agents. Smaller than lethal amounts produce few
serious effects.
Cyanide inhibits the cellular enzyme cytochrome oxidase to inhibit
oxygen metabolism and energy generation by the cell. Most signs and
symptoms are of central nervous system origin and after inhalation of
a large amount include a brief period of hyperpnea, seizures, a
decrease in breathing rate until apnea occurs, and cardiac arrhythmias
leading to death. After ingestion, with slower absorption, other
effects include vertigo, nausea, and a feeling of weakness.
First aid therapy consists of amyl nitrite by inhalation. If apnea is
present this drug must be given in a ventilator. Sodium nitrite and
sodium thiosulfate, both of which must be given intravenously, are
more definitive antidotes. Assisted ventilation with oxygen should
also be used.
Pulmonary Agents
Pulmonary agents cause pulmonary edema, but very few other effects.
These agents include phosgene (carbonyl chloride), a World War I
chemical warfare agent now widely used in industry, and
perfluroroisobutylene, a pyrolysis product of Teflon7. After
inhalation these compounds breakdown the alveolar-capillary
membrane which allows plasma to leak into the alveoli.
Potentially lethal pulmonary edema begins hours after exposure, with
symptoms of dyspnea and a productive cough.
Because the effects do not begin until hours after exposure (usually
four to 24 hours) the initial responder will see an asymptomatic
patient. A person with a history of possible exposure to one of these
compounds should be removed from the contaminated area and
should be kept at complete rest without even walking. Exertion will
increase the subsequent illness.
Incapacitating agents
Incapacitating agents are usually defined as chemical agents that
produce reversible disturbances in the central nervous system that
disrupt cognitive ability. The former military agent BZ (now used in
pharmacology where it is known as QNB) is a cholinergic blocking
compound and produces many effects similar to those of atropine,
such as mydriasis, drying of secretions, heart rate changes, and
decreased intestinal motility. BZ, after an onset time of an hour or
more, will--like high doses of atropine--produce confusion,
disorientation, and disturbances in perception (delusions,
hallucinations) and expressive function (slurred speech). The
antidote, physostigmine (Antilirium7), reverses these effects for about
an hour, and because the effects of BZ last for hours to days repeated
doses must be given.
MEDICAL RESPONSE
What can we as medical responders do about a terrorist attack?
Prevention and prophylaxis are commonly used in medicine to
prevent illness. However, these do not apply in this instance.
Prevention is what intelligence and law enforcement agencies do.
Medical personnel have neither the training nor resources to prevent a
terrorist attack. Prophylaxis, in the form of immunization, is a
common way to prevent disease, but there is no known prophylaxis
for chemical agents, and even if there were it would be impractical to
immunize a population at risk because we do not know what
population is at risk.
Medical personnel have the task of taking care of casualties after the
event has occurred. This includes diagnosis, management, and triage
of casualties while preventing spread of the disease or agent.
Preparation for this includes knowledge and equipment. The
responder must have knowledge of the agent, its effects, and
countermeasures and knowledge of how to protect self and others,
which includes decontamination of self and others. Equipment
includes material for countermeasures, such as antidotes if known,
and material for protection, such as protective clothing and masks.
How is all of this to be approached? Protective equipment should be
already in place in most hospitals and responder units because it is a
requirement under HAZMAT regulations, and the responder suits and
self-contained breathing apparatus used for HAZMAT operations is
generally quite adequate for chemical warfare agents. Knowledge of
casualty decontamination is also a requirement under HAZMAT
regulations, and the same techniques apply to chemical warfare agent
casualties.
In rural areas medical facilities there may be supplies of atropine and
2-PAMCl for use in insecticide poisoning, but in cities these supplies
are small at best. The antidotes for cyanide poisoning, sodium nitrite
and sodium thiosulfate, are generally not available in large amounts.
Is it cost effective to stock these antidotes in amounts adequate to
treat the number of casualties that might be expected in our larger
cities or for that matter in any town or city that might be a terrorist
target? This question must be addressed if we are to take terrorism
with chemical agents seriously.
Finally, there is knowledge of these agents, their effects, and methods
of counteracting these effects in casualties. Do civilian medical
responders have this knowledge? Generally not. Most know that the
nerve agents are similar to organophosphorous insecticides, and some
may have an idea of what to do for a cyanide casualty. But poisoning
by these compounds is uncommon in most parts of the country. In the
past, military chemical warfare agents have been considered a military
matter, not a concern for civilian medical personnel. The Tokyo
subway attack changed that. These agents might very quickly and
unexpectedly become a civilian concern, and civilians will have to
respond quickly.
Is there training on the medical aspects of these agents in the civilian
medical community? Currently not, except within the limited areas
surrounding military depots. Whether initiated on the federal, state,
or local level, this must be undertaken if one takes this threat
seriously. Is there readily available information on these agents? Is
there a single source of information to which a medical responder can
turn in the event of a terrorist attack with a chemical warfare agent?
Generally not unless the response unit is close to a military depot.
There should be such a reference source in each medical response
unit.
SUMMARY
Terrorists have used chemical warfare agents and may use them again.
These agents range from those that cause death quickly, such as the
nerve agents and cyanide, to those with effects beginning hours after
exposure, such as mustard and the pulmonary agents. Although
prevention of such an attack would be the best strategy, this may not
be possible. Medical personnel must be prepared to diagnose,
manage, and triage casualties. To do this, they must have equipment
and knowledge.
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