Initial effects after mild to moderate exposures to chlorine include ocular and
nasal irritation, followed by cough, and progressing to a choking sensation and
substernal chest tightness. Bronchospasm often occurs, especially in patients with
a history of reactive airway disease. Pulmonary edema may develop within 30
minutes to 4 hours depending on the severity of exposure.
Mild to moderate exposures to phosgene may be initially asymptomatic with
only the perception of a pleasant odor of newly mown hay. Thus, lung-exposure
time may be significant before victims remove themselves from the affected area.
Pulmonary edema occurs after a considerable delay, typically 4 to 6 hours, but up
to 24 hours after low concentration exposures. In these cases, delayed-onset
shortness of breath or chest tightness precedes objective clinical or radiologic
findings. With high concentration exposures, early lacrimation may be followed
by cough, dyspnea, and pulmonary edema. The pulmonary edema may be so
severe as to result in hypotension from hypovolemia. The onset of shortness of
breath or chest tightness within the first 4 hours of exposure to phosgene portends
the eventual development of massive pulmonary edema and a grave prognosis.
Management of exposure to pulmonary agents is primarily supportive.
Removal to fresh air generally suffices for decontamination. Careful attention to
control of pulmonary secretions, bronchospasm, and pulmonary edema as well as
to aggressive treatment of secondary bacterial infection (often occurring 3 to 5
days after exposure) is required. Animal studies suggest a modest benefit of
steroid therapy in mitigating lung injury after chlorine inhalation; thus steroids
may be considered for patients with chlorine exposure, especially as an adjunct to
bronchodilators. In addition, some symptomatic relief has also been reported for
chlorine exposure with nebulized 3.75% sodium bicarbonate therapy, but the
impact of this regimen on pulmonary damage is unknown.

Cyanide
Compounds containing the cyanide ion (CN− ) have a long history as favored
agents for homicide and suicide, but their efficacy as CWAs is limited by their
volatility in open air and by their flammability. However, if released

nonexplosively in a crowded, closed room, they could have devastating effects.
Chemical agents containing cyanide include the liquids hydrocyanic acid
(hydrogen cyanide, HCN; NATO Code AC) and cyanogen chloride (ClCN;
NATO code CK), both of which rapidly vaporize after release.
Toxicology
Some cyanide is normally present in human tissues and several pathways exist for
its metabolism. For example, cyanide reacts reversibly with metals such as ferric


ion (Fe3+ ) and cobalt; in the body, the reaction of hydroxocobalamin with
cyanide yields cyanocobalamin, or vitamin B12 . The ability of the body to
metabolize small quantities of cyanide, given sufficient time, accounts for the
dependence of cyanide toxicity on conditions of concentration and exposure time.
The same amount of cyanide that will kill when given over a few minutes may be
successfully metabolized by the body if administered over several hours. Doses of
cyanide large enough to overwhelm normal metabolism inhibit electron transport
of the mitochondrial cytochrome chain. The inactivation of this enzyme site
results in cellular anoxia and a decreased arteriovenous oxygen difference (from
inability of cells to use delivered oxygen), increased lactic acid (from accelerated
glycolysis under anaerobic conditions), and metabolic acidosis.
Clinical Manifestations
Clinical manifestations of cyanide poisoning relate to cellular anoxia; thus the
heart and brain are most severely affected. High concentrations of cyanide vapor
initially produce tachypnea, hyperpnea, and hypertension within 10 to 15
seconds. Anoxic injury to the CNS and myocardium soon follow, with
unconsciousness and seizures (30 seconds after exposure), opisthotonus, trismus,
facial muscle spasm, decerebrate posturing, bradycardia, dysrhythmias,
hypotension, and eventually cardiac arrest (as early as 4 to 8 minutes after
exposure).
Exposure to low concentrations of vapor produces nonspecific effects such as

headache, light-headedness, nausea, and ataxia. “Classic” signs of cyanide
poisoning are said to include severe dyspnea without cyanosis, flushing from
increased oxygen content venous blood, and a bitter almond odor to breath and
body fluids. Noteworthy laboratory abnormalities in cyanide poisoning include an
abnormally high mixed venous oxygen saturation with a resultant decreased
arteriovenous oxygen content difference (one of the most useful laboratory
indicators of cyanide poisoning), a high anion gap metabolic acidosis, and
hyperlactatemia.
Both cyanide and nerve-agent casualties can collapse suddenly, stop breathing,
and convulse. Gasping, normal or dilated pupil size (as opposed to miosis), pink
skin (instead of cyanosis), and normal secretions (as opposed to increased
secretions) may lead to a clinical diagnosis of cyanide over nerve agent, but none
of these signs is pathognomic. The similarities between cyanide and nerve-agent
casualties may be more apparent than the differences.
Management


Management of cyanide poisoning begins with removal to fresh air. Dermal
decontamination is unnecessary if exposure has been only to vapor, but wet
clothing should be removed and the underlying skin should be washed with soap
and water. Attention to the basics of intensive supportive care is critical and
includes administration of 100% oxygen to all significantly symptomatic patients,
mechanical ventilation as needed, circulatory support with crystalloid and
vasopressors, correction of metabolic acidosis with IV sodium bicarbonate, and
seizure control. The cyanide-induced inhibition of cellular oxygen use might lead
to the expectation that supplemental oxygen would not be of use in cyanide
poisoning, but in fact, administration of 100% oxygen has been found to
empirically exert a beneficial effect, possibly by affecting the interaction of
cyanide with nitric oxide in mitochondria.
Symptomatic patients, especially those with severe manifestations, may further

benefit from specific antidotal therapy. Currently, two regimens are available in
the United States. The first, the original “cyanide antidote kit” utilizes a two-step
process. First, a methemoglobin-forming agent such as amyl nitrite or sodium
nitrite is administered. This causes dissociation of bound cyanide from the
cytochrome oxidase and restores aerobic energy production. Perhaps even more
importantly, nitrites generate nitric oxide, which antagonizes the inhibition of
cytochrome oxidase by cyanide. The second step of the cyanide antidote kit is
provision of a sulfur donor, sodium thiosulfate, which reacts irreversibly with
cyanide to generate thiocyanate and sulfites, both of which are excreted in the
urine.
Caution is warranted when using this cyanide antidote. Nitrites result in
vasodilation, which may enhance vital organ perfusion. However, too rapid
infusion may cause or exacerbate hypotension, and overproduction of
methemoglobin may compromise oxygen-carrying capacity. Thus, this therapy
should be avoided in conscious patients with minimal symptoms and used with
caution in patients, especially children, whose cyanide toxicity may be
complicated by carbon monoxide poisoning (e.g., smoke-inhalation victims).
However, a case study of adult smoke-inhalation victims treated with nitrites and
sodium thiosulfate showed no complications of the nitrite therapy, and smoke
inhalation should be regarded as a relative rather than an absolute
contraindication to nitrite use.
The nitrite risk–benefit ratio becomes more favorable in the context of a
severely intoxicated casualty of a terrorist cyanide vapor attack, and careful
attention to proper dosing and rate of administration should allow safe use of this
antidote. Pediatric nitrite dosing depends on body weight and hemoglobin


concentration. The recommended initial pediatric dosage, assuming hemoglobin
concentration of 12 g/dL, is 0.33 mL/kg of the standard 3% sodium nitrite
solution, given slowly IV over 5 to 10 minutes; the initial adult dosage is 10 mL.

Thiosulfate itself is efficacious, relatively benign, and also synergistic with
oxygen administration. The initial thiosulfate dose for children is 1.65 mL/kg of
the standard 25% solution IV, and the initial adult dose is 50 mL. Second
treatments with one-half the initial dose of nitrite and thiosulfate may be given 30
minutes after the original dose if needed in severe cases.
The newer antidote available in the United States is hydroxocobalamin,
available in Cyanokit. This compound nonenzymatically and reversibly reacts
with cyanide to form cyanocobalamin (vitamin B12 ) which is subsequently
excreted. It does not induce hypotension (in fact, it predictably raises the blood
pressure) or methemoglobinemia and has been advocated as a replacement for the
cyanide antidote kit, especially for smoke-inhalation victims. However, the
cyanide antidote kit has a well-documented record of efficacy. Moreover,
hydroxocobalamin must be given via the IV route; amyl nitrite, included in the
cyanide antidote kit, can be given via inhalation to a patient without IV access.
The recommended initial dose of hydroxocobalamin is 5 g in adults or 70 mg/kg
in children, administered IV over 15 minutes (∼15 mL/min). A second 5-g dose
(70 mg/kg in children) may be repeated in severely affected patients, with the
second infusion rate ranging from 15 minutes to 2 hours based on the condition of
the patient. The medication is dark red in color, and treatment results in reddening
of skin and mucous membranes and red-colored urine that may last several days.
This phenomenon may also skew some common laboratory results that are based
on colorimetric tests, such as creatinine, bilirubin, and hepatic transaminases, as
well as cooximetry results.
To date, the superiority of one cyanide antidote over another has not been
clearly demonstrated. Newer compounds with oral availability are under
investigation and include cobinamide, a cobalamin precursor with high cyanide
affinity, and analogs of 3-methyl pyruvate, which like thiosulfate enhance
conversion of cyanide to thiocyanate. Because clinical distinction between
cyanide and nerve-agent casualties may be difficult, any patient thought to have
been exposed either to cyanide or to a nerve agent but who does not respond to

antidotal therapy specific for the suspected agent should be given a trial of the
antidotes for the other agent.

Riot-Control Agents