AC CK
Summary
Signs and Symptoms: Few. After exposure to high Ct: seizures, respiratory and cardiac arrest.
Detection: M256A1 Ticket. (NOT the M8A1 alarm and CAM.
Decontamination: Skin decontamination is usually not necessary because the agents are highly volatile. Wet, contaminated clothing should be removed and the underlying skin decontaminated with water or other standard decontaminates.
Management: Antidote: Intravenous sodium nitrite and sodium thiosulfate. Supportive: Oxygen; correct acidosis.
Cyanide is a rapidly acting lethal agent that is limited in
its military usefulness by its high LCt50 and high
volatility. Death occurs in 6 to 8 minutes after inhalation of a
high Ct. Sodium nitrite and sodium thiosulfate are effective
antidotes.
The French used about 4000 tons of cyanide in WWI without
notable military success, possibly because the small one- to
two-pound munitions used could not deliver the large amounts
needed to cause biological effects. Other factors included the
high volatility of cyanide (which quickly evaporated and
dispersed) and its "all or nothing" biological
activity, i.e., it caused few effects below the lethal Ct (this
is in contrast to mustard, which causes eye damage at 1% of the
lethal amount).
The U.S. maintained a small number of cyanide munitions during World War II (WWII). Japan allegedly used cyanide against China before and during WWII, and Iraq may have used cyanide against the Kurds in the 1980s.
Terms: The term cyanide refers to the anion CN-,
or to its acidic form, hydrocyanic acid (HCN). Cyanogen (C2N2)
is formed by the oxidation of cyanide ions; however, the term
cyanogen has also come to refer to a substance that forms cyanide
upon metabolism and produces the biological effects of free
cyanide (the term cyanogen is from "cyano" and
"gennan," Greek meaning "to produce"). A
simple cyanide (HCN, NaCN) is a compound that dissociates
to the cyanide anion (CN-) and a cation (H+,
Na+). A nitrile is an organic compound that
contains cyanide. A cyanogen usually refers to a nitrile
that liberates the cyanide anion during metabolism and produces
the biological effects of the cyanide anion. Cyanogens may be
simple (cyanogen chloride) or complex (sodium nitroprusside).
Cyanides are also called "blood agents," an
antiquated term still used by many in the military. At the time
of the introduction of cyanide in World War I, the other chemical
agents in use caused mainly local effects: riot control agents
injured the skin and mucous membranes from direct contact, and
phosgene damaged the lungs after inhalation. In contrast, cyanide
when inhaled produced systemic effects and was thought to be
carried in the blood; hence the term "blood agent." The
widespread distribution of absorbed nerve agents and vesicants
via the blood invalidates this term as a specific designator for
cyanide. Also, the use of "blood agent" for cyanide
connotes to some people that the site of action of cyanide is in
the blood, an erroneous notion.
Materials of interest as chemical agents are the cyanide hydrogen
cyanide (hydrocyanic acid; AC) and the simple
cyanogen, cyanogen chloride (CK). Cyanogen bromide
was used briefly in World War I, but is of no present interest.
Sources other than military: The cyanide
ion is ubiquitous in nearly all living organisms which tolerate
and even require the ion in low concentrations. The fruits and
seeds (especially pits) of many plants, such as cherries,
peaches, almonds, and lima beans, contain cyanogens capable of
releasing free cyanide following enzymatic degradation. The
edible portion (the roots) of the cassava plant (widely used as a
food staple in many parts of the world) is also cyanogenic. The
combustion of any material containing carbon and nitrogen has the
potential to form cyanide; some plastics (particularly
acrylonitriles) predictably release clinically significant
amounts when burned. Industrial concerns in the U.S. manufacture
over 300,000 tons of hydrogen cyanide annually. Cyanides find
widespread use in chemical syntheses, electroplating, mineral
extraction, dyeing, printing, photography, and agriculture, and
in the manufacture of paper, textiles, and plastics.
The cyanides are in liquid state in munitions, but rapidly
vaporize upon detonation of the munitions. The major threat is
from the vapor. The liquid toxicity is about that of mustard (see toxicity, below).
The preferred way to deliver cyanide is by large munitions
(bombs, large shells), because smaller weapons will not provide
the concentrations needed for effects.
Cyanide has a high affinity for certain sulfur compounds
(sulfanes, which contain two covalently bonded but unequally
charged sulfur atoms) and for certain metallic complexes,
particularly those containing cobalt and the trivalent form of
iron (Fe3+). The cyanide ion can rapidly combine with
iron in cytochrome a3 (a component of the cytochrome
aa3 or cytochrome oxidase complex in mitochrondria) to
inhibit this enzyme, thus preventing intracellular oxygen
utilization. The cell then utilizes anaerobic metabolism,
creating excess lactic acid and a metabolic acidosis. Cyanide
also has a high affinity for the ferric iron of methemoglobin and
one therapeutic strategem induces the formation of methemoglobin
to which cyanide preferentially binds.
The small quantity of cyanide always present in human tissues
is metabolized at the approximate rate of 17 Fg/kg"min,
primarily by the hepatic enzyme rhodanese, which catalyzes the
irreversible reaction of cyanide and a sulfane to produce
thiocyanate, a relatively nontoxic compound excreted in the
urine. (An elevated concentration of thiocyanate in either blood
or urine is evidence of cyanide exposure.) The limiting factor
under normal conditions is the availability of a sulfane as a
substrate for rhodanese, and sulfur is administered
therapeutically as sodium thiosulfate to accelerate this
reaction. Because of the ability of the body to detoxify small
amounts of cyanide via the rhodanese-catalyzed reaction with
sulfane, the lethal dose of cyanide is time dependent; that is, a
given amount of cyanide absorbed slowly may cause no biological
effects even though the same amount administered over a very
short period of time may be lethal. In contrast, the LCt50
of each of the other chemical agents, which are not metabolized
to the same extent as is cyanide, is relatively constant over
time, and a lethal amount causes death whether administered
within minutes or over hours.
Toxicities:
Cyanide is the least toxic of the "lethal" chemical
agents. The LCt50s of AC
and CK by inhalation have been estimated to be 2500-5000
mg"min/m3 for AC and about 11,000
mg"min/m3 for CK. LD50s
for hydrogen cyanide have been estimated to be 1.1 mg/kg for
intravenous administration and 100 mg/kg after skin exposure. The
oral LD50s for sodium and potassium
cyanide are about 100 and 200 mg/kg respectively.
Cyanide is unique among military chemical agents because it is
detoxified at a rate that is of practical importance, about 17
Fg/kg"min. As a result the LCt50 is greater for a
long exposure (e.g., 60 min) than for a short exposure (e.g., 2
min).
Effects: The organs most susceptible to
cyanide are the central nervous system (CNS) and the heart. Most
clinical effects are of CNS origin and are nonspecific.
About 15 seconds after inhalation of a high concentration of
cyanide vapor concentration there is a transient hyperpnea
followed in 15-30 seconds by the onset of convulsions.
Respiratory activity stops two to three minutes later, and
cardiac activity ceases several minutes later still, or at about
six to eight minutes after exposure.
The onset and progression of signs and symptoms after
ingestion of cyanide or after inhalation of a lower concentration
of vapor are slower. The first effects may not occur until
several minutes after exposure, and the time course of these
effects depends on the amount absorbed and the rate of
absorption. The initial transient hyperpnea may be followed by a
feelings of anxiety or apprehension, agitation, vertigo, a
feeling of weakness, nausea with or without vomiting, and
muscular trembling. Later, consciousness is lost, respiration
decreases in rate and depth, and convulsions, apnea, and cardiac
dysrhythmias and standstill follow. Because this cascade of
events is prolonged, diagnosis and successful treatment are
possible.
The effects of cyanogen chloride include those described for
hydrogen cyanide. Cyanogen chloride is also similar to the riot
control agents in causing irritation to the eyes, nose, and
airways as well as marked lacrimation, rhinorrhea, and
bronchosecretions.
Physical Findings: Physical findings are
few and non-specific. The two that are said to be characteristic
are in fact not always observed. The first is severe respiratory
distress in an acyanotic individual. When seen,
"cherry-red" skin suggests either circulating
carboxyhemoglobin from carbon monoxide poisoning or a high venous
oxygen content from failure of extraction of oxygen by tissues
poisoned by cyanide or hydrogen sulfide. However, cyanide victims
may have normal appearing skin and may even be cyanotic, although
cyanosis is not classically associated with cyanide poisoning.
Table: Cyanide (AC and CK)
Effects from vapor exposure
| Moderate, from low concentration | Transient increase in rate and depth of breathing, dizziness,nausea, vomiting, headache | These may progress to severe effects if exposure continues. | The time of onset of these effects depends on the concentration, but is often within minutes after start of exposure. |
| Severe, from high concentration | Transient increase in rate and depth of breathing --
15 seconds Convulsions -- 30 seconds Cessation of respiration -- 2-4 minutes Cessation of heartbeat -- 4-8 minutes |
In addition to the above, CK causes intense irritation of the
eyes, nose, and airways.
The second classic sign is the odor of bitter almonds. However, about 50% of the population is genetically unable to detect the odor of cyanide.
The casualty may be diaphoretic with normal sized or large pupils. An initial hypertension and compensatory bradycardia are followed by a declining blood pressure and tachycardia. Terminal hypotension is accompanied by bradyarrhythmias before asystole.
Effects begin in 15 seconds following inhalation of a lethal
Ct; death ensues in six to eight minutes. The onset of effects
following inhalation of lower Cts may be as early as minutes
after the beginning of the exposure. After exposure is terminated
by evacuation to fresh air or by masking, there is little danger
of delayed onset of effects.
Battlefield inhalational exposure to either cyanide or a nerve
agent may precipitate the sudden onset of loss of consciousness
followed by convulsions and apnea. The nerve agent casualty has
miosis (until shortly before death), copious oral and nasal
secretions, and muscular fasciculations. The cyanide casualty has
normal sized or dilated pupils, few secretions, and muscular
twitching but no fasciculations. In addition, the nerve agent
casualty may be cyanotic, and the cyanide casualty usually is not
cyanotic.
1. An elevated blood cyanide concentration: Mild effects may
be apparent at concentrations of 0.5-1.0 Fg/mL, and
concentrations of 2.5 Fg/mL and higher are associated with coma,
convulsions and death.
2. Acidosis: Metabolic acidosis with a high concentration of
lactic acid (lactic acidosis), or a metabolic acidosis with an
unexplained high anion gap (if the means to measure lactic acid
are not available) may be present. Because oxygen cannot be
utilized, anaerobic metabolism with the production of lactic acid
replaces aerobic metabolism. Lactic acidosis, however, may
reflect other disease states and is not specific for cyanide
poisoning.
3. Oxygen content of venous blood greater than normal. This
also is because of poisoning of the intramitochondrial
respiratory chain and the resulting failure of cells to extract
oxygen from arterial blood. This finding is also not specific for
cyanide poisoning.
The primary goal in therapy is to remove the cyanide from the
enzyme cytochrome a3 in the cytochrome oxidase
complex. A complicating factor is the rapidity with which
cyanide, particularly inhaled cyanide, causes death.
A secondary goal is to detoxify or bind the cyanide so that it
can not reenter the cell to reinhibit the enzyme. A closely
associated goal is supportive management.
Methemoglobin has a high affinity for cyanide, and cyanide
will preferentially bind to methemoglobin rather than to the
cytochrome. Most methemoglobin formers have clinically
significant side effects. The nitrites, which were first used to
antagonize the effects of cyanide over a century ago, cause
orthostatic hypotension, but this is relatively insignificant in
a supine casualty. Amyl nitrite, historically the first nitrite
used, is an volatile substance formulated in a perle that is
crushed or broken for the victim to inhale. In an apneic patient
a means of ventilation is necessary.
Another methemoglobin former, sodium nitrite, is formulated
for intravenous use. The standard ampule contains 300 mg of the
drug in 10 mL of diluent, and this is injected intravenously over
a two- to four-minute period.
Detoxification (metabolism) of cyanide is accomplished by the
administration of a sulfur-containing compound that combines with
cyanide to produce thiocyanate, a relatively non-toxic substance
which is rapidly excreted via the kidneys. The hepatic enzyme
rhodanese catalyzes the one-way reaction of cyanide and a sulfane
to thiocyanate. Sodium thiosulfate is packaged in a 50-mL ampule
containing 12.5 grams of the drug. Intravenous injection of all
12.5 grams follows successful completion of the intravenous
injection of sodium nitrite. Half of the original dosage of each
drug may be repeated if symptoms persist.
An immediate casualty is one who presents within
minutes of inhalational exposure with convulsions or the recent
onset of apnea, but with circulation intact. Immediate antidote
administration will be lifesaving.
A minimal casualty is one who has inhaled less than a
lethal amount and has mild effects. The antidotes may reduce his
symptoms, but are not lifesaving.
The delayed casualty is one recovering from mild
effects or from successful therapy. Generally, it will be hours
before full recovery. Evacuation is not necessary, but might be
considered until full recovery takes place.
An expectant casualty is apneic with circulatory
failure.
Generally, a casualty who has had inhalation exposure and
survives long enough to reach medical care will need little care.
Full recovery is usually relatively fast after cyanide intoxication. Those with mild to moderate effects from the agent can usually return to duty within hours, and those successfully treated after severe effects can return within a day.