agents are a group of highly toxic organic esters of phosphoric acid
derivatives. These agents have physiological effects (inhibition of
cholinesterase) resembling those of physostigmine and pyridostigmine. However,
they are more potent, longer-acting, and tend to be irreversible after a time
which varies with the agent.
agents are among the deadliest of chemical agents and may produce rapid
symptoms. They include the G- and V-agents. Examples of G-agents are Tabun (GA),
Sarin (GB), Soman (GD), and GF. A V-agent is VX. In some countries,
"V" agents are known as "A" agents.
agents can be dispersed by artillery shell, mortar shell, rocket, land mine,
missile, aircraft spray, and aircraft bomb or bomblet.
related but somewhat less toxic compounds have proven to be useful in medicine
and agriculture, as indicated below. The symptoms and treatment of poisoning by
these compounds are similar to those of poisoning by nerve agents.
agents have been used in the treatment of abdominal distention, urinary
retention, and glaucoma.
of the insecticides currently in use are organophosphates and are chemically
related to nerve agents. Although beneficial for arthropod control, their
widespread use has caused many accidental poisonings - some fatal.
Organophosphate insecticides may have a slower and longer lasting effect as
compared to CW organophosphates.
and Chemical Properties
agents are colorless to light brown liquids. Some are volatile, while others are
relatively non-volatile at room temperature. Most nerve agents are essentially
odorless; however, some have a faint fruity odor. In toxic amounts, aqueous
solutions of nerve agents are tasteless. The G-agents tend to be nonpersistent,
whereas the V-agents are persistent. However, thickened nonpersistent agents may
present a hazard for an extended period of time. These agents are moderately
soluble in water with slow hydrolysis; are highly soluble in lipids; and are
rapidly inactivated by strong alkalies and chlorinating compounds (strong
alkalies and chlorinating compounds are used for decontaminating equipment; in
diluted formulas, chlorinating compounds are used for patient de-contamination).
of and Protection Against Nerve Agents
agents may be absorbed through any body surface. When dispersed as a spray or
aerosol, droplets can be absorbed through the skin, eyes, and respiratory tract.
When dispersed as a vapor at expected field concentrations, the vapor is
primarily absorbed through the respiratory tract. If enough agent is absorbed,
local effects are followed by generalized systemic effects. The rapidity with
which effects occur is directly related to the amount of agent absorbed in a
given period of time. Liquid nerve agents may be absorbed through the skin,
eyes, mouth, and membranes of the nose. Nerve agents may also be absorbed
through the gastrointestinal tract when ingested with food or water. Local
effects after skin exposure are localized sweating and/or muscular twitching.
Local effects after vapor or liquid exposure to the eye include miosis and often
conjunctival hyperemia. Local effects of liquid on the mucous membrane include
twitching or contracting of the underlying muscle and glandular secretions. Ab-sorption
of a nerve agent by any route may result in generalized systemic effects. The
respiratory tract (inhalation) is the most rapid and effective route of
protective mask and hood protect the face and neck, eyes, mouth, and respiratory
tract against nerve agent spray, vapor, and aerosol. Nerve agent vapor (in
expected field concentrations) is absorbed through the skin very slowly, if at
all, so proper masking may protect against the effects of low vapor
concentrations. To prevent inhaling an incapacitating or lethal dose, hold your
breath and put on your mask within 9 seconds at the first warning of a nerve
nerve agents penetrate ordinary clothing rapidly. However, significant
absorption through the skin requires a period of minutes. The effects may be
reduced by quickly removing contaminated clothing and neutralizing liquid nerve
agent on the skin (washed off, blotted, or wiped away). Prompt decontamination
of the skin is imperative. Decontamination of nerve agents on the skin within 1
minute after contamination is perhaps ten times more effective than it would be
if delayed 5 minutes. A nerve agent on the skin can be removed effectively by
using the M291 Skin Decontaminating Kit or the M258A1 Skin Decontamination Kit
(app D). The M291 Skin Decontaminating Kit is replacing the M258A1. Upon receipt
of the M291, discontinue using the M258A1 on the skin. Liquid nerve agent in the
eye is absorbed faster than on the skin and is extremely dangerous; immediately
irrigate the eye with copious amounts of water.
chemical protective overgarment, patient protective wrap (PPW), impermeable
protective gloves, and overboots protect the skin against nerve agents in
liquid, aerosol, and vapor forms.
of Nerve Agents
of Action. The effects of nerve agents (table 1-1) are due to their ability
to inhibit cholinesterase enzymes throughout the body. Since the normal function
of these enzymes is to hydrolyze acetylcholine wherever it is released, such
inhibition results in the accumulation of excessive concentrations of
acetylcholine at its various sites of action. These include the endings of the
autonomic nerves to the smooth muscle of the iris, ciliary body, bronchial tree,
gastrointestinal tract, bladder, and blood vessels; to the salivary glands and
secretory glands of the gastrointestinal tract and respiratory tract; and to the
cardiac muscle and endings of sympathetic nerves to the sweat glands (fig 1-1).
The accumulation of acetylcholine at these sites results in characteristic
muscarinic signs and symptoms (table 1-1). The accumulation of acetylcholine at
the endings of motor nerves to voluntary muscles and in some autonomic ganglia
results in nicotinic signs and symptoms (table 1-1). Finally, the accumulation
of excessive acetylcholine in the brain and spinal cord results in
characteristic CNS symptoms (table 1-1). The inhibition of cholinesterase
enzymes throughout the body by nerve agents may be irreversible and their
effects prolonged; therefore, treatment should begin promptly before
irreversibility occurs. Until the tissue cholinesterase enzymes are restored to
normal activity, there is a period of increased susceptibility to the effects of
another exposure to any nerve agent. This period of increased susceptibility
occurs during the enzyme regeneration phase which could last from weeks to
several months, depending on the severity of the initial exposure. During this
period the effects of repeated exposures are cumulative.
Aside from the decrease in the activity of cholinesterase enzymes throughout the
body (which may be analyzed by laboratory methods), no specific lesions are
detectable by ordinary gross examination. At postmortem examination there is
usually capillary dilation, hyperemia, and edema of the lungs; there may be
similar changes in the brain and the remaining organs. Neuropathologic changes
have been reported in animals following severe intoxication.
of Vapor. The lungs and the eyes absorb nerve agents rapidly. Changes occur
in the smooth muscle of the eye, resulting in miosis (contraction of the pupil);
also in the smooth muscle and secretory glands of the bronchi, producing
bronchial constriction and excessive secretions in the upper and lower airways.
In high vapor concentrations, the nerve agent is carried from the lungs
throughout the circulatory system; widespread systemic effects may appear in
less than 1 minute.
ocular effects. These effects begin within seconds or minutes after exposure
and before there is any evidence of systemic absorption. The earliest ocular
effect which follows minimal symptomatic exposure to vapor is miosis. This is an
invariable sign of ocular exposure to enough vapor to produce symptoms. It is
also the last ocular manifestation to disappear. The pupillary constriction may
be different in each eye. Within a few minutes after the onset of exposure,
there also occurs redness of the eyes due to conjunctival hyperemia and a
sensation of pressure with heaviness in and behind the eyes. Usually vision is
not grossly impaired, although there may be a slight dimness especially in the
peripheral fields or when in dim or artificial light. Exposure to a level of a
nerve agent vapor slightly above the minimal symptomatic dose results in miosis;
pain in and behind the eyes attributable to ciliary spasm, especially on
focusing; some difficulty of accommodation; and frontal headache. The pain
becomes worse when the casualty tries to focus the eyes or looks at a bright
light. Some twitching of the eyelids may occur. Occasionally there is nausea and
vomiting which, in the absence of systemic absorption, may be due to a reflex
initiated by the ocular effects. These local effects may result in moderate
discomfort and some loss of efficiency, but may not necessarily produce
casualties. Following minimal symptomatic exposure, the miosis lasts from 24 to
72 hours. After exposure to at least the minimal symptomatic dose, miosis is
well established within half an hour. Miosis remains marked during the first day
after exposure and then diminishes gradually over 2 to 3 days after MODERATE
exposure, but may persist for as long as 14 days after severe exposure. The
conjunctival erythema, eye pain, and headache may last from 2 to 15 days
depending on the dose.
respiratory effects. Following minimal exposure, the earliest effects on the
respiratory tract are watery nasal discharge, nasal hyperemia, sensation of
tightness in the chest, and occasionally, prolonged wheezing expiration
suggestive of bronchoconstriction or increased bronchial secretion. The
rhinorrhea usually lasts for several hours after minimal exposure and for about
1 day after more severe exposure. The respiratory symptoms are usually
intermittent for several hours duration after MILD exposure; they may last for 1
or 2 days after more severe exposure.
Table 1-1. Signs and Symptoms of Nerve Agent Poisoning
Miosis, marked, usually
maximal (pinpoint), sometimes unequal. Frontal headache, eye pain on
focusing, blurring of vision. Rhinorrhea, hyperemia. Tightness in chest,
bronchoconstriction, increased secretion, cough. Occasional nausea and
Systemic Absorption (depending on dose)
Tightness in chest,
with prolonged wheezing expiration suggestive of bronchoconstriction or
increased secretion, dyspnea, pain in chest, increased bronchial
secretin, cough, cyanosis, pulmonary edema.
vomiting, abdominal cramps, epigastric and substernal tightness (cardiospasm)
with "heartburn" and eructatin, diarrhea, tenesmus,
Easy fatigue, mild
weakness, muscular twitching, fasciculatins, cramps, generalized
weakness/flaccid paralysis (including muscles of respiration) with
dyspnea and cyanosis.
elevation of blood pressure followed by hypotension.
3. Central Nervous
Effects: Generalized weakness, depression of respiratory and circulatory
centers with dyspnea, cytanosis, and hypotension, convulsion, loss of
consciusness, and coma.
Systemic effects. The
sequence of symptoms varies with the route of exposure. While respiratory
symptoms are generally the first to appear after inhalation of nerve agent
vapor, gastrointestinal symptoms are usually the first after ingestion.
Following comparable degrees of exposure, respiratory manifestations are most
severe after inhalation and gastrointestinal symptoms may be most severe after
ingestion. Otherwise, the systemic manifestations are, in general, similar after
any exposure to nerve agent poisoning by any route. If local ocular exposure has
not occurred, the ocular manifestations (including miosis) initially may be
absent. The signs, symptoms, and their time course following exposure to nerve
agent are given in table 2-2. The systemic effects may be considered to be
nicotinic, muscarinic, or by any action at receptors within the CNS. The
predominance of muscarinic, nicotinic, or CNS effects will influence the amount
of atropine, oxime, or anticonvulsant which must be given as therapy. These
effects will be considered separately.
effects. The tightness in the chest is an early local symptom of respiratory
exposure. This symptom progressively increases as the nerve agent is absorbed
into the systemic circulation, whatever the route of exposure. After MODERATE or
severe exposure, excessive bronchial and upper airway secretions occur and may
become very profuse, causing coughing, airway obstruction, and respiratory
distress. Audible wheezing may occur, with prolonged expiration and difficulty
in moving air into and out of the lungs, due to the increased bronchial
secretion or to bronchoconstriction, or both. Some pain may occur in the lower
thorax and salivation increases. Bronchial secretion and salivation may be so
profuse that watery secretions run out of the sides of the mouth. The secretions
may be thick and tenacious. If postural drainage or suction is not employed,
these secretions may add to the airway obstruction. Laryngeal spasm and collapse
of the hypopharyngeal musculature may also obstruct the airway. The casualty may
gasp for breath, froth at the mouth, and become cyanotic.-If the upper airway
becomes obstructed by secretions, laryngeal spasm, or hypopharyngeal musculature
collapse, or if the bronchial tree becomes obstructed by secretions or
bronchoconstriction, little ventilation may occur despite respiratory movements.
As hypoxemia and cyanosis increase, the casualty will fall exhausted and become
unconscious. Following inhalation of nerve agent vapor, the respiratory
manifestations predominate over the other muscarinic effects; they are likely to
be most severe in older casualties and in those with a history of respiratory
disease, particularly bronchial asthma. However, if the exposure is not so
overwhelming as to cause death within a few minutes, other muscarinic effects
appear. These include sweating, anorexia, nausea, and epigastric and substernal
tightness with heartburn and eructation. If absorption of the nerve agent has
been great enough (whether due to a single large exposure or to repeated smaller
exposures), there may follow abdominal cramps, increased peristalsis, vomiting,
diarrhea, tenesmus, increased lacrimation, and urinary frequency. Cardiovascular
effects are occasional early bradycardia, transient tachycardia and/or
hypertension followed by hypotension, and cardiac arrhythmias. The casualty
perspires profusely, may have involuntary defecation and urination, and may go
into cardiorespiratory arrest followed by death.
effects. With the appearance of MODERATE muscarinic systemic effects, the
casualty begins to have increased fatigability and MILD generalized weakness
which is increased by exertion. This is followed by involuntary muscular
twitching, scattered muscular fasciculations, and occasional muscle cramps. The
skin may be pale due to vasoconstriction and blood pressure moderately elevated
(transitory) together with tachycardia, resulting from epinephrine response to
excess acetylcholine. If the exposure has been severe, the muscarinic
cardiovascular symptoms will dominate and the fascicular twitching (which
usually appear first in the eyelids and in the facial and calf muscles) becomes
generalized. Many rippling movements are seen under the skin and twitching
movements appear in all parts of the body. This is followed by severe
generalized muscular weakness, including the muscles of respiration. The
respiratory movements become more labored, shallow, and rapid; then they become
slow and finally intermittent. Later, respiratory muscle weakness may become
profound and contribute to respiratory depression. Central respiratory de-pression
may be a major cause of respiratory failure.
nervous system effects. In MILD exposures, the systemic manifestations of
nerve agent poisoning usually include tension, anxiety, jitteriness,
restlessness, emotional lability, and giddiness. There may be insomnia or
excessive dreaming, occasionally with nightmares. If the exposure is more
marked, the following symptoms may be evident: headache, tremor, drowsiness,
difficulty in concentration, memory impairment with slow recall of recent
events, and slowing of reactions. In some casualties, there is apathy,
withdrawal, and depression. With the appearance of MODERATE symptoms,
abnormalities of the electroencephalogram occur, characterized by irregularities
in rhythm, varia-tions in potential, and intermittent bursts of abnormally slow
waves of elevated voltage similar to those seen in patients with epilepsy. These
abnormal waves become more marked after 1 or more minutes of hyperventilation
which, if prolonged, may occasion-ally precipitate a generalized convulsion. If
absorption of nerve agent has been great enough, the casualty becomes confused
and ataxic. The casualty may have changes in speech (consisting of slurring,
difficulty in forming words, and multiple repetition of the last syllable). The
casualty may then become comatose, reflexes may disappear, and respiration may
become Cheyne-Stokes in character. Finally, generalized convulsions may ensue.
With the appearance of severe CNS symptoms, central respiratory depression will
occur (adding to the respiratory embarrassment that may already be present) and
may progress to respiratory arrest. However, after severe exposure, the casualty
may lose consciousness and promptly convulse without other obvious symptoms.
Death is usually due to respiratory arrest and anoxia. Prompt initiation of
assisted ventilation may prevent death. Depression of the circulatory centers
may also occur, resulting in a marked reduction in heart rate with a fall of
blood pressure some time before death.
of Liquid Nerve Agent
ocular effects. The local ocular effects are similar to the effects of nerve
agent vapor. If the concentration of the liquid nerve agent contaminating the
eye is high, the effects will be instantaneous and marked; and, if the exposure
of the two eyes is unequal, the local manifestations may be unequal. Hyperemia
may occur but there is no immediate local inflammatory reaction such as may
occur following ocular exposure to more irritating substances (for example,
skin effects. Following cutaneous exposure, there is localized sweating at
and near the site of exposure and localized muscular twitching and
fasciculation. However, these may not be noticed causing the skin absorption to
go undetected until systemic symptoms begin.
gastrointestinal effects. Following the ingestion of substances containing a
nerve agent (which is essentially tasteless), the initial symptoms include
abdominal cramps, vomiting, and diarrhea.
effects. The sequence of symptoms varies with the route of exposure. While
respiratory symptoms are generally the first to appear after inhalation of a
nerve agent vapor, gastrointestinal symptoms are usually the first after
ingestion. Following comparable degrees of exposure, respiratory manifestations
are most severe after inhalation, and gastrointestinal symptoms may be most
severe after ingestion. Otherwise, the systemic manifestations are, in general,
similar after any exposure to nerve agent poisoning by any route. If local
ocular exposure has not occurred, the ocular manifestations (including miosis)
initially may be absent.
1-2. Time Course of Effects of Nerve Agents.
EFFECTS APPEAR AFTER EXPOSURE
OF EFFECTS AFTER MILD EXPOSURE
OF EFFECTS AFTER SEVERE EXPOSURE
nasal hyperemia, tightness in chest, wheezing
One to several minutes
A few hours
1 to 2 days
conjunctival hyperemia, eye pain, frontal headache
One to several minutes
2 to 3 days
Respiratory or eyes
nicotinic, and central nervous system effects (see table 1-1)
Less than 1 minute to a
few minutes after moderate or severe exposure; about 30 minutes after
Several hours to a day
Acute effects: 2 to 3
days; CNS effects: days to weeks
Same as vapor effects
Similar to effects of
(see table 1-1)
About 30 minutes after
Several hours to a day
2 to 5 days
Local sweating and
3 minutes to 2 hours
(see table 1-1)
1 to 5 days
Same as for vapor
2 to 4 days
15 minutes to 2 hours
2 to 5 days
(see table 1-1)
15 minutes to 2 hours
3 to 5 days
Effects of Repeated Exposure. Daily
exposure to concentrations of a nerve agent insufficient to produce symptoms
following a single exposure may result in the onset of symptoms after several
days. Continued daily exposure may be followed by increasingly severe effects.
After symptoms subside, increased susceptibility may persists for up to 3
months. The degree of exposure required to produce recurrence of symptoms and
the severity of these symptoms depend on the dose received and thetime interval
since the last exposure. Increased susceptibility is notlimited to the
particular nerve agent initially absorbed.
of Death. In the absence of treatment, death is caused by anoxia resulting
from airway obstruction, weakness of the muscles of respiration, and central
depression of respiration. Airway obstruction is due to pharyngeal muscular
collapse; upper airway and bronchial secretions; bronchial constriction and
occasionally laryngospasm; and paralysis of the respiratory muscles. Respiration
is shallow, labored, and rapid, and the casualty may gasp and struggle for air.
Cyanosis increases. Finally, respiration becomes slow and then ceases resulting
in unconsciousness. The blood pressure (which may have been transitorily
elevated) falls. Cardiac rhythm may become irregular and death may ensue. The
individual may survive several lethal doses of a nerve agent if assisted
ventilation is initiated via cricothyroidotomy or endotracheal tube, if airway
secretions are cleared by postural drainage and suction, and if secretions and
bronchial constrictions are diminished by the vigorous administration of
atropine. However, if the exposure has been overwhelming, amounting to many
times the lethal dose, death may occur as a result of respiratory arrest and
cardiac arrhythmia despite treatment. When overwhelming doses of the agent are
absorbed quickly, death occurs rapidly without orderly progression of symptoms.
of Nerve Agent Poisoning
agent poisoning may be identified from the characteristic signs and symptoms. If
exposure to vapor has occurred, the pupils will be very small, usually
pinpointed. If exposure has been cutaneous, or has followed ingestion of a nerve
agent in contaminated food or water, the pupils may be normal or, in the
presence of severe systemic symptoms, slightly to moderately reduced in size. In
this event, the other manifestations of nerve agent poisoning must be relied on
to establish the diagnosis. No other known chemical agent produces muscular
twitching and fasciculations, rapidly developing pinpoint pupils, or the
characteristic train of muscarinic, nicotinic, and CNS manifestations.
important that all service members know the following MILD and SEVERE signs and
symptoms of nerve agent poisoning. Service members who have most or all of the
symptoms listed below must IMMEDIATELY receive first aid (self-aid or buddy aid)
(paras 1-11a and b, respectively).
poisoning (self-aid). Casualties with MILD symptoms may experience most or
all of the following:
(b) Unexplained sudden headache.
(c) Sudden drooling.
(d) Difficulty in seeing (dimness of vision and miosis).
(e) Tightness in the chest or difficulty in breathing.
(f) Wheezing and coughing.
(g) Localized sweating and muscular twitching in the area of the contaminated skin.
(h) Stomach cramps.
(i) Nausea with or without vomiting.
(j) Tachycardia followed by brady-cardia.
symptoms (buddy aid). Casualties with SEVERE symptoms may experience most or
all of the MILD symptoms, plus most or all of the following:
or confused behavior.
(b) Increased wheezing and increased dyspnea (difficulty in breathing).
(c) Severely pinpointed pupils.
(d) Red eyes with tearing.
(f) Severe muscular twitching and general weakness.
(g) Involuntary urination and defeca-tion.
(j) Respiratory failure.
with severe symptoms WILL NOT be able to treat themselves and MUST RECEIVE
prompt buddy aid, CLS aid prompt follow-on medical treatment if they are to
with MODERATE poisoning will experience an increase in the severity of most or
all of the MILD symptoms. Especially prominent will be fatigue, weakness, and
muscle fasciculations. The progress of symptoms from MILD to MODERATE indicates
either inadequate treatment or continuing exposure to the agent.
AND TREATMENT OF NERVE AGENT POISONING
Elements of Prevention and Treatment
essential prevention and treatment elements of nerve agent poisoning are
Donning the protective mask and hood at the first indication of a
nerve agent attack.
Administering the MARK I (para 1-11) as soon as any signs or
symptoms are noted.
Administering the CANA to MODERATE to severely poisoned casualties
The U.S. Navy does not use the MARK I.Instead, the Navy issues three atropine
and three pralidoxime chloride (2 PAM C1) autoinjectors per person.
Removing or neutralizing any liquid contamination immediately.
Removing airway secretions if they are obstructing the airway.
Airway suction may be needed.
Establishing a patent airway (for example, with a cricothyroidotomy or
endotracheal tube) and administering assisted ventilation, if required. Oxygen
is desired, if available.
respiratory tract absorbs nerve agent vapor very rapidly. The protective mask
must be put on IMMEDIATELY when it is suspected that nerve agent vapor is
present in the air. Hold the breath until the mask is on, cleared, and checked.
If the nerve agent concentration in the air is high, a few breaths may result in
the inhalation of enough nerve agent to be incapacitating or even lethal. When
the concentration in the air is low, a longer exposure may precede the onset of
symptoms and the detection of nerve agent poisoning. Since the effects of a
nerve agent are progressive and cumulative, the prevention of further absorption
is urgent once symptoms have begun. Protective masks should be worn until the
"all clear" signal is given.
give nerve agent antidotes for preventive purposes BEFORE contemplated exposure
to a nerve agent. To do so may enhance respiratory absorption of nerve agents by
inhibiting bronchoconstriction and bronchial secretion. Atropine will degrade
performance when taken in doses of more than 2 milligram (mg) without nerve
agent exposure, especially when maximal visual acuity is required. Also,
atropine will degrade an individual's ability to perform duties in a hot
environment. Atropine is rapidly used up in the treatment of nerve agent
poisoning. A person incapacitated by nerve agent poisoning will likely remain
incapacitated since atropine will not reverse all the signs and symptoms of
poisoning, even in large doses.
agents (liquid or vapor) can poison food and water. For details on management
and decontamination of food and water, see FM 8-10-7.
of Nerve Agent Antidotes
Atropine. Atropine sulfate remains an essential drug in the
treatment of nerve agent poisoning. It acts by blocking the effects of
acetylcholine at muscarinic receptors and produces relief from many of the
symptoms previously listed. If given in large doses, some therapeutic effects
are also produced within the CNS although atropine does not readily penetrate
the blood-brain barrier as does diazepam (para 2-8a(3) ), and central muscarinic
receptors are thought not to be identical with those in the periphery. It is
thought to counteract the respiratory depression in the medulla oblongata. Used
alone, it has little influence on the mortality rate in the potentially fatal
apneic cases for which assisted ventilation is many times more effective.
However, the combination of adequate Atropinization plus assisted ventilation is
several times more effective in saving lives than assisted ventilation alone.
2 PAM Cl. 2 PAM Cl is an oxime which increases the effectiveness of
drug therapy in poisoning by some - but not all- cholinesterase inhibitors.
Unlike atropine, 2 PAM Cl acts by blocking the nerve agent inhibition of
cholinesterase and/or reactivating the inhibited acetylcholinesterase clinically
at muscarinic sites. Thus 2 PAM Cl relieves the skeletal neuromuscular block, as
well as reactivating the acetylcholinesterase clinically at muscarinic sites.
The role of 2 PAM Cl is to block and reverse the bonding of the nerve agent to
the acetylcholinesterase. Oximes must be given early in the poisoning; after a
short period of time (different for each type of nerve agent), they may no
longer be effective.
2 PAM Cl varies in its effectiveness against nerve agents. It is least effective
Diazepam. Diazepam readily crosses the blood-brain barrier to block
the effects of acetylcholine on the CNS, in contrast to the partial protection
of atropine at best. Diazepam antagonizes the convulsive action of nerve agents.
The addition of diazepam to the basic antidotes prevents or ameliorates
convulsions in MODERATE to severe nerve agent poisoning.
Atropine. A 2-mg intramuscular (IM) injection will reach peak
effectiveness in 3 to 10 minutes, then blood concentrations will decline. If the
system is unchallenged by a nerve agent, a 2-mg IM injection will cause atropine
effects for several hours. In the presence of a nerve agent challenge, the
effectiveness of atropine is markedly reduced and the duration of the agent is
significantly shortened. More frequent doses of atropine will be required to
achieve and maintain Atropinization.
2 PAM Cl. Depending on the degree of intoxication, a 600-mg IM will
be effective in 6 to 8 minutes and will maintain peak effectiveness for 1 hour
or more. If the system is unchallenged by a nerve agent, a 600-mg IM will remain
in the circulatory system for several hours without apparent effect.
Diazepam. A 10-mg IM injection in the thigh ordinarily produces
significant plasma levels in 10 minutes; peak plasma concentrations are obtained
in about 1 hour. The concentrations will then decline over a prolonged period.
Rapid administration of diazepam by IM autoinjector after nerve agent exposure
may more effectively prevent or ameliorate convulsions. SEVERE nerve agent
toxicity may require multiple 10-mg doses given at about 10 minute intervals for
a maximum of three (3) injections (a total of 30 mg diazepam) to control
Produced by the Antidotes
administration of a single dose of 2 mg (one autoinjector) of atropine to an
individual who has absorbed minimal or no nerve agent produces MILD symptoms,
including dryness of the skin, mouth, and throat, with slight difficulty in
swallowing. The individual may have a feeling of warmth, slight flushing, rapid
pulse, some hesitancy of urination, and an occasional desire to belch. The
pupils may be slightly dilated but react to light. In some individuals, there
may be MILD drowsiness and slowness of memory and ability to recall. Recipients
of atropine may have the feeling that their movements are slow and their near
vision is blurred. Some individuals may be mildly relaxed. These symptoms should
not interfere with ordinary activity, except in the oc-casional individual who
proves to be unusually reactive to the "sensation" effects of atropine
(particularly the feeling of drowsiness). However, mental reaction may be
slightly slowed down (for this reason, aviators must not fly an aircraft after
taking atropine until cleared by the flight surgeon). If the administration of 2
mg of atropine is repeated within an hour with-out nerve agent challenge, the
symptoms become MODERATE. In most of these individuals, there will be some CNS
symptoms (such as drowsiness, fatigue, slowness of memory and ability to recall,
the feeling that body movements are slow, and blurred near vision); but they can
continue ordinary activity with some loss of efficiency. Near vision may be
impaired for as long as 24 hours. After repeated injections of atropine,
heat-stressed individuals will become casualties ((b) below). A third 2-mg dose
of atropine (again without nerve agent challenge) admin-istered within an hour
will result in severe symptoms which will not permit ordinary activity - in
fact, most individuals will be incapacitated. SEVERE incapacitating symptoms of
overAtropinization (nerve agent antidote poisoning) are a very dry mouth;
swelling of the tongue and oral mucous membranes; difficulty in swallowing;
thirst; hoarseness; dry and flushed skin; dilated pupils; blurred near vision;
tachycardia (rapid pulse); urinary retention (in older individuals); con-stipation;
slowing of mental and physical activity; restlessness; headache; disorientation;
hallucinations; depression; increased drowsiness; extreme fatigue; rapid
respiratory panting; and respiratory distress. Abnormal behavior may require
restraint. The effects of atropine without nerve agent challenge are fairly
prolonged, lasting 3 to 5 hours after one or two injections and 12 to 24 hours
after marked over-Atropinization. OverAtropinization may be incapacitating but
presents little danger to life in a temperate environment for the nonheat-stressed
individual. A single dose of 10 mg of atropine has been administered
intravenously to normal young adults without endangering life-even in the
absence of any prior absorption of a nerve agent-although it has produced very
marked signs of overdose.
While an unchallenged dose of atropine may allow individuals to continue normal
duties, they must be closely monitored for possible heat injury. This is
especially important when at MOPP 4 and the in-dividuals' ability to perspire is
reduced due to atropine.
hot, desert, or tropical environ-ments or in heat-stressed individuals, doses of
atropine tolerated well in temperate climates may be seriously incapacitating by
interference with the sweating mechanism. This can sharply reduce the combat
effectiveness of troops who have suffered little or no exposure to a nerve
agent. In hot climates or in heat-stressed individuals, one dose (2 mg) of
atropine can reduce efficiency. Two doses (4 mg) will sharply reduce combat
efficiency, and 6 mg will incapacitate troops for several hours. In hot, humid
climates, individuals who have inadvertently taken an overdose of atropine and
are exhibiting signs of atropine intoxication should have their activity
restricted. In addition, these casualties must be kept as cool as possible for 6
to 8 hours after injection to avoid serious incapacitation. Usually, the
casualties will recover fully in 24 hours or less from a significant overdose of
in chemical operations has shown that when troops become alarmed, some believe
they have been exposed to more chemical agents than they actually have been.
Hence, it is important that service members NOT give themselves more than one
atropine injection (2 mg). Casualties who are able to ambulate and know who they
are and where they are WILL NOT need any more atropine injections. If the
symptoms do recur additional atropine, up to two more injections for a total of
three (3) , can be administered to these casualties. A service member must
consult with a buddy to determine if he or she needs additional injections of
atropine. If an individual's heart rate is above 90, breathing appears normal,
bronchial secretions have diminished, and the skin is dry, the individual does
not need anymore atropine at this time. Additional atropine is given by a buddy
since casualties requiring more will be unable to administer additional
injections to themselves. The additional administration of atropine to a service
member with only MILD symptoms must be approached cautiously with at least 10 to
15 minutes elapsing between successive injections. If the signs of nerve agent
poisoning (para 2-5) disappear, or if signs of Atropinization, such as a heart
rate above 90, diminished bronchial secretions, and dry skin, appear during one
of these 10- to 15-minute periods, no further injections should be administered.
These casualties should remain under observation without further injections of
atropine unless signs of nerve agent intoxication reappear.
Although one means of determining the casualty's need for additional atropine is
the heart rate, assessing his or her respiratory effort is important in the
evaluation. Labored breathing, including coughing, noisy breathing, wheezing,
and gasping for air, indicates the need for administering additional atropine.
When the heart rate is not obtainable, the need for additional atropine may be
based on the degree of respiratory impairment. When adequate atropine has been
given, labored breathing efforts will be relieved. This assessment must be
performed without compromising the protective posture of MOPP.
with severe symptoms due to systemic absorption of a nerve agent have increased
tolerance for atropine. Multiple doses may be required before signs of
Atropinization appear, such as heart rate above 90, diminished bronchial
secretions, and dry skin. Large doses are required to ameliorate the muscarinic
effects of nerve agent poisoning. The absence of increased tolerance for
atropine indicates that nerve agent poisoning probably is not present or is MILd.
In the presence of severe nerve agent poisoning, as much as 50 mg of atropine
may be required for treatment in a 24-hour period. More than three injections of
atropine will be administered only by the CLS or medical personnel.
visual changes may be a side effect of 2 PAM Cl. After the administration of
three injections of 2 PAM Cl, generally no further oxime benefit is attained by
additional injections of 2 PAM Cl.
administration of a single dose of 10 mg (one autoinjector of CANA) to an
individual who has absorbed minimal or no nerve agent produces significant
performance decrements for about 2 to 5 hours. The individual will have impaired
vision and decision-making functions over this time period. Overall alertness
may be impaired. There could also be breathing difficulty. For this reason,
casualties should be lying on their side until they are alert again. There may
be transient irritation, as well as pain, at the injection sites.
BUDDY AID, COMBAT LIFESAVER PROCEDURES, AND COMBAT MEDIC/CORPSMAN TREATMENT
of Self-Aid and Buddy Aid
protective mask and hood must be put on IMMEDIATELY at the first signs of a
chemical attack. (The protective overgarment should have already been put on
prior to the use of chemicals on the battlefield.) Stop breathing, put on your
mask, clear and seal the mask, and resume breathing. Secure the mask hood. The
mask and protective clothing are worn continually until the "all
clear" signal is given.
mask any casualty that does not have a mask on if the atmosphere is still
appearance of nerve agent poisoning symptoms calls for the immediate IM
injection of the nerve agent antidote (paras 1-11 and 1-12). Since inhalation
will be the most common route of exposure, the most likely initial symptom will
be rhinorrhea (runny nose), then miosis (dim vision), followed by a feeling of
tightness or constriction in the chest. After ocular (eyes) splash, there will
be immediate miosis. After cutaneous (skin) splash, the initial systemic
symptoms may be localized sweating and localized muscular twitching, followed by
nausea and abdominal cramps. After ingestion, the first symptoms are likely to
be nausea and vomiting. In any case, use the nerve agent antidotes as directed (paras
1-11 and 1-12).
remove any liquid nerve agent on the skin, on the clothing, or in the eyes.
If a liquid nerve agent gets on the skin, decontamination must be
accomplished within 1 min-ute (see app D). Then continue the mission. Examine
the contaminated area occasionally for local sweating and muscular twitching. If
these occur, the nerve agent antidote should be administered. Combat duties
should be continued, as systemic symptoms of nerve agent poisoning may not occur
or may be MILD if the decontamination was done immediately and successfully.
If a drop or splash of liquid nerve agent gets into the eye,
instant action is necessary to avoid serious effects. Irrigate the eye
immediately with water as described in appendix d. During the next minute, the
pupil of the contaminated eye should be observed by a buddy. If the pupil
rapidly gets smaller, a nerve agent antidote should be administered. If the
pupil does not get smaller, the ocular contamination was not caused by a nerve
agent and atropine is not needed.
good relief is obtained from one set of MARK I injections and breathing is
normal, carry on with combat duties. Dryness of the mouth is a good sign-it
means enough atropine has been taken to overcome the dangerous effects of the
nerve agent. If symptoms of the nerve agent are not relieved, the service member
should be administered two more sets of the MARK I injections plus one injection
of CANA by a buddy, in accordance with the provisions of paragraph 1-11. If
symptoms still persist and the pulse (heart rate) drops below 90 per minute,
bronchial secretions persist, or the skin remains moist, then the service member
can be administered additional atropine injections by the CLS or medical
personnel (who carry additional atropine for the treatment of nerve agent
casualties) to maintain adequate Atropinization. The CLS and com-bat
medic/corpsman also carry extra CANA for ad-ministration to nerve agent
casualties (para 1-12). The CLS or combat medic/corpsman can administer
additional CANA up to a maximum of three before evacuating the casualty.
Evacuate the service member to a field MTF as soon as the combat situation
and 2 PAM Cl by injection do not relieve the local effects of nerve agent vapor
on the eyes. Although the eyes may hurt and there may be difficulty in focusing
and a headache, the service members should carry on with their duties to the
best of their ability. These symptoms are annoying but not dangerous.
to high concentrations of a nerve agent may bring on incoordination, mental
confusion, and/or collapse so rapidly that the casualty cannot perform self-aid.
If this happens, the nearest able service member must render buddy aid.
nerve agent exposure may rapidly cause unconsciousness, muscular paralysis, and
the cessation of breathing. When this occurs, antidote alone will not save life.
IMMEDIATELY after a buddy administers three sets of the MARK I and CANA,
assisted ventilation must be started by medical personnel, if a resuscitation
device is available. Assisted ventilation should be continued until normal
breathing is restored.
Nerve Agent Antidote Kit, MARK I
Nerve Agent Antidote Kit, MARK I (fig E-1), is an antidote used by the Army and
the Air Force in the treatment of nerve agent poisoning.
The MARK I kit consists of four separate components: the atropine autoinjector,
the 2 PAM C1 autoinjector, the plastic clip, and the foam carrying case.
The atropine autoinjector consist of a hard plastic tube containing
2 mg (0.7 milliliter (ml)) of atropine in solution. It has a pressure activated
coiled spring mechanism which triggers the needle for injection of the antidote
solution. The container is white plastic with yellow lettering on green
identification and directions labels. The safety cap is yellow plastic attached
to the clip at the rear of the container. The needle end is a green plastic cap
which, when pressure is applied, activates the spring mechanism.
The 2 PAM Cl autoinjector is a hard plastic tube which dispenses
600 mg/2 ml of 2 PAM Cl (300 mg/ml) solution when activated. It has a pressure
activated coiled spring mechanism identical to that in the atropine autoinjector.
The container is clear plastic with black lettering on a brown identification
label. Directions are in black lettering on a white background. The safety cap
is gray plastic attached to the clip at the rear of the container. The needle
end is black plastic.
The clip is made of clear hard plastic constructed to hold the pair
of autoinjectors together while attached to their safety caps. The safety caps
are held flush to the bottom of the plastic clip by a movable metal retaining
flange. The clip container recesses are labeled with black numbers:
"1" for the atropine and "2" for the 2 PAM Cl autoinjector.
The foam envelope is a charcoal gray form-fitting case with pressed
seams and is designed to carry both autoinjectors. The envelope is used for
shipping purposes only and is removed by service members prior to putting the
MARK I kits in their mask carrier.
Issue to Service Members. In the U.S. Army and the U.S. Air Force,
each person is authorized to carry three sets of the MARK I kit for the
treatment of nerve agent poisoning. The U.S. Navy, however, does not use the
MARK I but, rather, its antidote components are issued as three atropine and
three 2 PAM Cl autoinjectors per person.
Protection Against Freezing. The atropine and the 2 PAM Cl
solutions freeze at about 30°F (1°C). Therefore, when the temperature is below
freezing, the MARK I injectors should be protected against freezing.
Autoinjectors issued to the individual service member are normally carried in
the protective mask carrier. During cold weather when the temperature is below
freezing, the injectors should be carried in an inside pocket close to the body.
(Should the MARK I injectors become frozen, they can be thawed and used. )
in the Use of the Nerve Agent Antidote Kit, MARK I
following are principles to be followed in the administration of the MARK I (fig
If you experience most or all of the MILD symptoms of nerve agent poisoning (para
2-5), you should IMMEDIATELY hold your breath (DO NOT INHALE) and put on your
protective mask. Then administer one set of MARK I injections into your lateral
thigh muscle (or buttocks). (Self-aid procedure for administering the
autoinjectors is found in app e. )
10 to 15 minutes after giving your-self the first set of injections since it
takes that long for the antidote to take effect. If you are able to ambulate,
know who you are, and where you are, you WILL NOT need a second set of MARK I
Giving yourself a second set of injections may create a nerve agent antidote
over-dose, which could result in incapacita-tion.
symptoms of nerve agent poisoning are not relieved after administering one set
of MARK I injections, seek someone else to check your symptoms. A buddy must
administer the second and third sets of injections, if needed.
Aid. If you encounter a service member suffering from SEVERE signs of nerve
agent poisoning (para 2-5), render the following aid:
Mask the casualty, if necessary. Do not fasten the hood.
Administer, in rapid succession, three sets of the MARK I. Follow
administration procedures outlined in appendix e.
Use the casualty's own antidote auto-injectors when providing aid. Do not use
your injectors on a casualty. If you do, you may not have any antidote available
when needed for self-aid.
Lifesaver. The CLS must check to verify if the individual has received three
sets of the MARK I. If not, the CLS performs first aid as described for buddy
aid above. If the individual has received the initial three sets of MARK I, then
the CLS may administer additional atropine injections at approximately 15 minute
intervals until Atropinization is achieved (that is a heart rate above 90 beats
per minute; reduced bronchial secretions; and reduced salivations). Administer
additional atropine at intervals of 30 minutes to 4 hours to maintain
Atropinization or until the casualty is placed under the care of medical
personnel. Check the heart rate by lifting the casualty's mask hood and feeling
for a pulse at the carotid artery. Request medical assistance as soon as the
tactical situation permits.
Medic/Corpsman. A casualty has received three sets of MARK I; however,
Atropinization has not been achieved. Administer additional atropine at
approximately 15 minute intervals until Atropinization is achieved (that is a
heart rate above 90 beats per minute; reduced bronchial secretions and reduced
salivations). Administer additional atropine at intervals of 30 minutes to 4
hours to maintain Atropinization or until the casualty is evacuated to an MTF.
Check the heart rate by lifting the casualty's mask hood and feeling for a pulse
at the carotid artery. Provide assisted ventilation for severely poisoned
casualties, if equipment is available. Monitor the patient for development of
in the Use of Convulsant Antidote for Nerve Agents
following are principles to be followed in the administration of CANA (fig E-1).
The CANA is NOT for use as self-aid. If you know who you are, where you are, and
what you are doing, you do not need CANA. If symptoms do not subside after
self-administering one MARK I, seek assistance from a buddy.
Aid. In addition to administering the MARK I antidotes for nerve agents as buddy
aid, also administer the CANA.
Mask the casualty, if necessary. Do not fasten the hood.
the CANA with the third MARK I to prevent convulsions. DO NOT administer more
than one CANA. Follow administration procedures outlined in appendix e.
DO NOT use your own CANA on the casualty. You may not have any antidote for your
own treatment, if needed.
Lifesaver and Medic/Corpsman. The CLS or medic/corpsman should administer
additional CANA to casualties suffering convulsions. Administer a second, and if
needed, a third CANA at 5 to 10 minute intervals for a maximum of three
injections (30 mg diazepam). Follow the steps and procedures described in buddy
aid for administering the CANA. DO NOT give more than two additional injections
for a total of three (one buddy aid plus two by CLS or medic/corpsman).
effect of atropine administration on MILD and MODERATE cases of nerve agent
poisoning may help confirm the diagnosis. Atropine injection alleviates most of
the muscarinic manifestations. It has little effect on the CNS symptoms and no
effect on the nicotinic symptoms. If the casualty has absorbed little or no
nerve agent, the administration of a single dose of 2 mg of atropine produces
symptoms of mild Atropinization (tachycardia, dry mouth) in most individuals and
repetition of this dose within 1 or 2 hours produces MODERATE symptoms of
Atropinization in almost all individuals. In contrast, a casualty with MODERATE
symptoms of nerve agent poisoning will not develop symptoms of Atropinization
after administration of 2 mg of atropine. A casualty with severe symptoms of
nerve agent poisoning may tolerate-indeed may require-considerably more than 4
mg of atropine (as much as 50 mg in 24 hours).
of Convulsant Antidote for Nerve Agents
(CANA) is intended to prevent or ameliorate convulsions in MODERATE to severe
nerve agent poisoning. A casualty with severe nerve agent poisoning may require
multiple doses of CANA (30 mg or more).
IN THE FIELD (MEDICAL TREATMENT FACILITY)
of the Nerve Agent Antidotes
arrival at the MTF a casualty is still presenting signs/symptoms of nerve agent
poisoning (para 2-5). The casualty has received self-aid, buddy aid, CLS care,
or treatment by the combat medic/corpsman, or other medical personnel in the
field before and during evacuation. Additional injections of the nerve agent
antidote(s) must be administered at the field MTF.
Atropinization should have been achieved before the casualty is evacuated to an
MTF; if not, then atropine is administered as follows:
symptoms should be treated by administering 2 mg of the atropine every 15
minutes until signs of Atropinization (dry mouth and skin, with cleared
pulmonary secretions) are achieved. Maintain Atropinization until muscarinic
symptoms should be treated by administering 2 mg of the atropine every 10 to 15
minutes until Atropinization is achieved. Maintain Atropinization by injecting 2
mg of atropine as often and long as needed.
symptoms should be treated by administering 2 mg of atropine as frequently as
required until Atropinization is achieved. Maintain Atropinization by injecting
2 mg of atropine every 10 to 30 minutes as long as needed.
Smoking should be prohibited until the symptoms of nerve agent poisoning have
Cl. Specifically as an adjunct to atropine, 2 PAM Cl may be used to increase the
effectiveness of therapy in poisoning by some, but not all nerve agents. An
important facet of the activity of 2 PAM Cl in such therapy is the reduced
duration of required assisted ventilation.
symptoms should have been treated by administering at least one 600-mg IM
injection of 2 PAM Cl.
symptoms should have been treated by administering one or more 600-mg IM
injections of 2 PAM Cl.
symptoms should have been treated by administering three 600-mg IM injections of
2 PAM Cl. Repeat the dose at least every hour if respiration has not improved.
Generally, no increased oxime benefit is obtained after three injections of 2
Diazepam is used specifically as a prevention of or treatment for convulsions in
nerve agent poisoned casualties. If brain damage is to be prevented in MODERATE
to severe nerve agent poisoned casualties, CANA must be administered early.
Seizures should be anticipated in all MODERATE to severe cases and treated with
the CANA and repeated as necessary.
of Follow-on Medical Treatment
following medical treatment may also be administered in a CPS or a clean
(uncontaminated) environment, depending on the patient's needs. Modifications of
these procedures may be used in a contaminated environment although an increase
in exposure will occur. The alternative of not performing these procedures is
death of the patient.
of Additional Atropine. For patients who are in severe respiratory distress or
are convulsing, all three sets of their MARK I autoinjectors should have been
given. (Convulsions are treated with diazepam, as described in c below.) If
relief does not occur and bronchial secretions and salivation do not decrease,
administer additional atropine as often as needed. In severe nerve agent
poisoning, the effect of each 2-mg atropine injection may be transient, lasting
only 5 to 15 minutes. Therefore, these patients must be closely observed and
atropine repeated at intervals that relieve (or counteract) the muscarinic
effects of the nerve agent and maintain mild Atropinization for as long as
of Bronchial Secretions and Salivation. Patients having excessive airway
secretions and salivation (an indication for additional atropine) should be
lying on their side, with the foot of the litter or bed elevated, if possible,
to promote drainage. If airway obstruction is occurring, the collar should be
loosened, the tongue pulled out, and the saliva and mucus cleared periodically
from the mouth and pharynx by suction. Then an oropharyngeal airway may be
inserted and suction carried out intermittently, as needed (through and around
the airway). If, despite concentrated efforts to carry out assisted ventilation,
the upper airway remains obstructed and adequate exchange of air does not occur,
insert an endotracheal tube. High airway resistance because of bronchial
constrictions and secretions may be decreased with the administration of
of Convulsions. Severely poisoned casualties that develop convulsions usually
progress rapidly to unconsciousness and generalized muscular weakness or flaccid
paralysis, at which point external evidences of convulsions cease. Seizures
should be anticipated in all MODERATE to severe cases and expectantly treated
with CANA/diazepam and repeated as necessary. Seizing is a prominent feature of
nerve agent poisoning, especially Gd. Administer CANA until seizures are
of Ocular Symptoms. Ocular symptoms produced by local absorption of a nerve
agent do not respond to the systemic administration of atropine. However,
minimal pain relief may be obtained by the local instillation of atropine
sulfate ophthalmic ointment (1 percent), repeated as needed at intervals of
several hours for 1 to 3 days. If local ocular effects of a nerve agent are
present, the size of the pupils cannot be used as an indicator of the systemic
effects of the nerve agent or the atropine.
Lavage. If water or food contaminated with a nerve agent has been ingested,
colicky abdominal pains, substernal tightness, increased salivation, and perhaps
nausea and vomiting will occur 1/2 hour or later. If ingestion is known to have
occurred, early gastric lavage with water should be done.
of Liquid Nerve Agent. Any liquid nerve agent on the skin or in the eyes should
be removed immediately.
Ventilation. If respiration is severely impaired or if it ceases after
administration of atropine, cyanosis will ensue and death will occur within
minutes unless immediate effective assisted ventilation is begun and maintained
until spontaneous respiration is resumed. Far forward in the field, a
cricothyroidotomy is the most practical means of providing an airway for
assisted ventilation, using a hand-powered ventilator equipped with an NBC
filter. When a casualty reaches an MTF where oxygen and a positive pressure
ventilator is available, these should be employed continuously until adequate
spontaneous respiration is resumed. An endotracheal tube will most likely be
Treatment outlined in paragraphs 1-15 and 1-16 is based on the U.S. Army
doctrine on the use of the MARK I and CANA (diazepam). These procedures do not
address the uniqueness of other environments (such as the threat in naval
operations) where alternatives may be more constrained, requiring modification
in the procedures. Procedures to address these variations should be issued by
the services concerned in accordance with their specific needs.