Chemical Overview
Organophosphates are a
diverse, and widely stocked, group of chemical agents available
in liquid, gas or aero-sol form. The military forms, known
as nerve agents/gases, are absorbed through the skin or lungs,
usually within 20-30 minutes. There are two types: G-agents
(non-persistent, death by inhala-tion), and V-agents (persistent,
death by inhalation or skin, conjunctival, and mucosal absorption).
Military grade nerve agents are Tabun
(GA), Sarin (GB), Soman (GD) and VX. The more widely
available organophosphates include common pesticides for home
and farm use. Of these,tetraethyl
pyrophosphate (TEPP) and parathion have caused numerous
deaths.
Tabun (GA) (O-ethyl dimethylamido-phosphorylcyanide),
the fi rst nerve gas, was developed in 1936 at IG Farben,
Germany. It is the easiest to manu-facture, as the necessary
chemicals are available on the open market.
Sarin (GB) (isopropyl methylphosono-fl uoridate) is
a colorless, odorless vola-tile liquid, soluble in water,
fi rst synthe-sized at IG Farben in 1938. It kills main-ly
through inhalation. Cyclosarin(GF)and
Thiosarin are variants.
Soman (GD) (pinoacolyl methylphos-phonofl uoiridate)
is the fastest-killing nerve gas, fi rst produced in 1944
at IG Farben. It is lethal through both inhala-tion and skin
contact.
VX (O-ethyl S-diisopropylaminomethyl
methylphosphonothiolate) is an odor-less, colorless, sticky
liquid, soluble in water <10°C, which easily passes
through the human skin. Discovered in the United Kingdom in
1952, the U.S. military began its production as a weapon in
1961. It is lethal through both inhalation and skin
Long-term Medical
Sequelae
Full recovery can take up to 3 months and, following recovery,
increased susceptibility may persist for up to 3 months. Persistent
paralysis, organophosphate induced delayed neuropathy (OPIDN),
and axonal death followed by demyelination, have been reported
in animal exposures to Sarin, but not in humans to date.
Environmental
Sequelae
Tabun lasts 1-2 days (weather
dependant), takes 20 times as long as water to evaporate and
persists in water one day at 20°C and six days at 5°C. Sarin has little persistence,
evaporating as fast as water or kerosene. Soman lasts 1-2 days (weather dependant) and takes 4 times as long
as water to evaporate. Thickeners can extend its persistence. VX can persist for weeks
to months, particularly in temperatures near or below 0°C,
and evaporates 1,500 times slower than Sarin.
Prophylaxis
For pretreatment (prophylaxis), a reversible anticholinesterase
agent, pyridostigmine, is recommended at a dose of 30 mg,
3 times daily, to produce a blood cholinesterase inhibition
of about 30%. In severe poisonings, this 30% level of inhibition
will allow the spontaneous reactivation of these inhibited
cholinesterases and the recuperation of the victim.
Disclaimer
Information contained in this fact sheet was current as of
August 2002, and was designed for educational purposes only.
Medication information should always be researched and verified
before initia-tion of patient treatment.
Source: CSB&EI—Centers For The Study Of Bioterrorism & Emerging Infections
Protective Equipment/Detection
Semi-permeable, active carbon containing, protective clothing and
a full-face gas mask with appropriate filter are the only gear that
can fully protect against nerve agents. If unavailable, protective
gowns, masks, and gloves can minimize skin exposure.Single and three-color
detector papers are available for individual use to detect liquid
nerve agent. Area detectors and monitoring devices are also available
through military or emergency management contacts.
Decontamination
Tabun, Sarin, Soman, and VX hydrolyze rapidly in strongly alkaline
or chlorinated solutions. Decontamination procedures for skin, equipment
and material include active neutralizing chemicals (chloramine solutions,
5% bleach) or neutral adsorbing powders (Fullers earth). Copious
amounts of water can also dilute and remove these agents. The victim’s
body fl uids, urine and feces do not present a hazard. Safe removal
and containment of the victim’s clothing is essential and decontamination is critical to prevent
healthcare workers from becoming casualties.
Signs and Symptoms
Nerve agents and organophosphate insecticides inhibit tissue cholinesterases
at synaptic sites, and cause the accumulation of excess acetylcholine
at nicotinic and muscarinic receptors. The earliest signs depend
upon route of exposure: respiratory signs if inhaled, GI disturbances
if ingested, and local skin signs with skin contact, although respiratory
distress quickly predominates in moderate to severe exposures. In
such exposures, if death is delayed, the muscarinic effects become
dominant, followed by the nicotinic effects. If there is no eye
contact, the ocular signs may come later in the progression of symptoms.
Symptoms following inhalation are immediate, while symptoms following
mild skin exposure can be delayed as much as 18 hours.
The estimated LCt50s
by inhalation are 400 mg-min/m3 for Tabun, 100 mg-min/m3 for Sarin, 50 mg-min/m3 for Soman and 10 mg-min/m3 for VX. Percutaneous LD50s
are 1000 mg, 1700 mg, 350 mg, and 6-10 mg, respectively.
Following a localized skin exposure expect meiosis, usually pinpoint
and sometimes unequal; frontal headache; nausea and vomiting; weakness;
and fasciculations or sweating at the exposure site. With severe
exposures, you will also note eye pain on focusing; dimmed vision;
rhinorrhea; chest tightness; wheezing suggestive of increased secretions
and bronchoconstriction; cough; generalized muscular twitching,
weakness, or paralysis; convulsions; loss of consciousness; and
loss of bladder and bowel control.
Following a mild inhalation exposure expect meiosis, dimmed vision,
headache, rhinorrhea, salivation, and dyspnea with chest tightness.
In severe exposures, you will also note slight chest pain; increased
bronchial secretions; pulmonary edema; cyanosis; anorexia; abdominal
cramps; “heartburn” and eructation; diarrhea; tenesmus;
involuntary defecation; increased sweating, salivation, and lacrimation;
slight bradycardia; urinary frequency; involuntary micturition;
easy fatigue; muscular twitching; fasciculations; generalized weakness,
including respiratory muscles; pallor; occasional elevation of blood
pressure; giddiness; anxiety or jitteriness; emotional lability;
excessive dreaming; insomnia; nightmares; apathy; withdrawal and
depression; drowsiness; difficulty in concentrating; slowness of
recall; confusion; slurred speech; ataxia; and, ultimately, coma,
with absence of reflexes; Cheyne-Stokes respiration; convulsions;
depression of respiratory and circulatory centers; and hypotension.
Besides symptomatology, measurement of decreased cholinesterase
activity in blood is the only presently available method for rapid
diagnosis of exposure to nerve agents. However, such testing is
non-specific and is only useful when >20% cholinesterase inhibition
is present. At that point, severe meiosis, headache, eye pain, conjunctival
hyperemia, rhinorrhea, and chest tightness are already evident.
Treatment
Full recovery may occur after a single, mild to moderate exposure.
However, repeated daily exposures are cumulative and may result
in severe poisoning. Moderate to severe poisonings necessitate treatment
for survival, as inhibition of acetylcholinesterase rapidly becomes
more or less irreversible.
First aid for nerve agent victims is basic. Remove them from additional
exposure. Flush the eyes with copious amounts of water for 10-15
minutes. Decontaminate the skin with liquid household bleach and
flush with water. For ingestions, administer activated charcoal
and a cathartic. DO NOT induce vomiting. If needed, begin CPR, avoiding
direct mouth-mouth contact.
The mainstays of treatment are anticholinergic and anticonvulsant
agents. Atropine sulfate, an antimuscarinic agent, blocks the parasympathetic
effects in the periphery and partially counteracts the convulsive
effects and respiratory depression in the CNS. Loading doses range
between 1 and 5 mg IV every 30 minutes until full atropinization
(dry mouth, skin, and bronchi; and heart rate >90 per minute),
and maintenance should continue for at least 24 hours at doses between
0.5 and 2 mg/hr. Be aware of potential arrhythmias secondary to
the atropine. Titration of atropine in the individual patient is
based on producing a decrease in bronchial constriction and secretions.
Heart rate changes are easier to follow but less important. Besides
atropine, a central acting anticonvulsant should be given, with
diazepam (10mg IM initially) being the preferred agent. Assisted
ventilation and general supportive measures will also be required,
sometimes for several days
Oximes, which are acetylcholinesterase reactivators, relieve the
important nicotinic symptoms of skeletal neuromuscular blockade.
Most clinical experience is with pralidoxime chloride (2-PAM, Protopam
chloride R), pralidoxime methanesulfonate (P2S) or methylsulfate
(Contrathion R ), and obidoxime chloride (Toxogonin R ). These agents
have poor CNS penetration and must be repeatedly injected or given
as a loading dose followed by a maintenance dose.
Additional information and references available at www.bioterrorism.slu.edu.
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