CG
Summary
Signs and Symptoms: Eye and airway irritation, dyspnea, chest tightness, and delayed pulmonary edema.
Detection: Odor of newly mown hay or freshly cut grass or corn. There is no military detector for phosgene.
Decontamination: Vapor: fresh air. Liquid: copious water irrigation.
Management: Termination of exposure, ABCs of resuscitation, enforced rest and observation, oxygen with or without positive airway pressure for signs of respiratory distress, other supportive therapy as needed.
Inhalation of selected organohalides, oxides of nitrogen (NOx),
and other compounds can result in varying degrees of pulmonary
edema, usually after a symptom-free period that varies in
duration with the amount inhaled. Chemically induced acute lung
injury by these groups of agents involves a permeability defect
in the blood-air-barrier (the alveolar-capillary membrane);
however, the precise mechanisms of toxicity remain an enigma. The
U.S. produces over a billion pounds of phosgene (CG) per year for
industrial uses; however, we do not stockpile this agent for
military use.
Perfluoroisobutylene (PFIB) is a toxic pyrolysis product of
tetrafluoroethylene polymers encountered in military materiel
(e.g., Teflon7, found in the interior of many military vehicles).
The oxides of nitrogen (NOxs) are components of blast
weapons or may be toxic decomposition products. Smokes, e.g., HC,
contain toxic compounds that cause the same effects as phosgene
does. The remainder of this chapter will deal solely with
phosgene because it is the prototype of this class of agents;
however, the principles of medical management of phosgene
exposure also apply to casualties from compounds such as PFIB or
NOxs.
Phosgene was first synthesized by John Davy in 1812.
Subsequent development as a potential chemical warfare agent led
to the first battlefield use of phosgene (in shells filled solely
with phosgene) at Verdun in 1917 by Germany. Later, both sides in
the conflict employed phosgene either alone or in mixed-substance
shells, usually in combination with chlorine. Although military
preparations for World War II included the manufacture and
stockpiling of phosgene-filled munitions, phosgene was not used
during that war, and the U.S. Armed Forces do not currently
stockpile this agent.
Phosgene is transported as a liquid. Military dispersion
during World War I followed the explosion of liquid filled shells
with subsequent rapid vaporization and formation of a white cloud
due to its slight solubility in an aqueous environment. It
spontaneously converted to a colorless, low-lying (density 4 x
air) gas. Because of its relatively low boiling point (7.5E C),
phosgene was often mixed with other substances. It has a
characteristic odor of sweet, newly mown hay.
Phosgene is only slightly soluble in water and aqueous
solutions. However, once dissolved it rapidly hydrolyzes to form
carbon dioxide and hydrochloric acid. The early-onset ocular,
nasal, and central airway irritation from high concentrations of
phosgene is caused by hydrochloric acid released during phosgene
hydrolysis; however, the carbonyl group (C=O) readily
participates in acylation reactions with amino (-NH2),
hydroxyl (-OH), or sulfhydryl (-SH) groups and these reactions
account for the major pathophysiological effects of phosgene.
These acylations occur at alveolar- capillary membranes and lead
to leakage of fluid from those capillaries into the interstitial
portions of the lung. This effect is from direct contact of
phosgene with these membranes; phosgene exposure by other routes,
e.g., by intravenous administration, does not cause this damage.
Phosgene-induced leakage of fluid from capillaries into the
pulmonary interstitium is normally opposed by lymphatic drainage
from the parenchyma, but as the fluid leakage increases, normal
drainage mechanisms become progressively overwhelmed. After a 20
minute to 24-hour long asymptomatic or latent period, fluid
eventually reaches alveoli and peripheral airways, leading to
increasingly severe dyspnea and clinically evident pulmonary
edema.
Toxicities: The odor threshold for
phosgene is about 1.5 mg/m3, and phosgene irritates
the mucous membranes at 4 mg/m3. The LCt50
is about 3200 mg·min/m3.
Effects: Phosgene produces pulmonary
edema following a clinical latent period of variable length that
depends primarily on the intensity of exposure (i.e., the Ct) but
also partly on the physical activity of the exposed individual.
After the latent period, the patient experiences worsening
respiratory distress that at first is unaccompanied by
objectively verifiable signs of pulmonary damage but that may
progress relentlessly to pulmonary edema and death.
During the time preceding the appearance of shortness of
breath, individuals exposed to particularly high concentrations
of organohalides may report symptoms associated with mucous
membrane irritation. Exposure to large quantities of phosgene may
irritate moist mucous membranes, presumably because of the
generation of hydrochloric acid from the hydrolysis of phosgene.
Transient burning sensation in the eyes with lacrimation and
chemical conjunctivitis may coexist with mild, early-onset cough
and a substernal ache with a sensation of pressure. Irritation of
the larynx by very large concentrations of the agent may lead to
sudden laryngeal spasm and death.
A clinical latent period during which the patient is
asymptomatic may follow low Ct exposure or may follow the
transient irritation associated with substantial phosgene
exposure. This asymptomatic period may persist up to 24 hours
after organohalide inhalation. The duration of this latent period
is shorter following high Ct's and is shortened by physical
exertion following exposure.
The most prominent symptom following the clinical latent
period is dyspnea, perceived as shortness of breath with or
without chest tightness. These sensations reflect hypoxemia,
increased ventilatory drive, and decreased lung compliance, all
of which result from the accumulation of fluid in the pulmonary
interstitium and peripheral airways. Fine crackles appear at the
lung bases, but these may not be clearly audible unless
auscultation is conducted after a forced expiration. Later,
auscultation reveals coarse crackles and r>les in all lung
fields, and increasing quantities of thin, watery secretions are
noted. The buildup of fluid in the lungs has two clinically
pertinent effects: First, developing pulmonary edema interferes
with oxygen delivery to alveolar capillaries and may lead to
hypoxemia, and if a sufficient percentage of hemoglobin is
unoxygenated cyanosis will become apparent. Secondly, the
sequestration of plasma-derived fluid (up to one liter per hour)
in the lungs may lead to hypovolemia and hypotension, interfering
with oxygen delivery to the brain, kidneys, and other crucial
organs. Death results from respiratory failure, hypoxemia,
hypovolemia, or a combination of these factors. Hypoxia and
hypotension may progress particularly rapidly and suggest a poor
prognosis. The development of symptoms and signs of pulmonary
edema within four hours of exposure is an especially accurate
indicator of a poor prognosis; in the absence of immediately
available intensive medical support, such patients are at high
risk of a fatal outcome. Complications include infection of
damaged lungs and delayed deaths following such respiratory
infections.
Phosgene is distinguished by its odor, its generalized
mucous-membrane irritation in high concentrations, dyspnea, and pulmonary
edema of delayed onset.
Riot control agents produce a burning sensation predominantly
in the eyes and upper airways. This irritation is typically more
intense than that caused by phosgene and is unaccompanied by the
distinctive odor of phosgene.
Nerve agents induce the production of watery secretions as
well as respiratory distress. However, their other characteristic
effects distinguish nerve agent toxicity from organohalide
inhalational injury.
The respiratory toxicity associated with vesicants is usually
delayed but predominantly affects the central rather than the
peripheral airways. Vesicant inhalation severe enough to cause
dyspnea typically causes signs of airway necrosis, often with
pseudomembrane formation and partial or complete upper airway
obstruction. Finally, pulmonary parenchymal damage following
vesicant exposure usually manifests itself as hemorrhage rather
than pulmonary edema.
No commonly available laboratory tests exist for the specific
identification or quantitation of phosgene inhalation; however,
an increase in the hematocrit may reflect the hemoconcentration
induced by transudation of fluid into the pulmonary parenchyma.
Arterial blood gases may show a low PaO2 or PaCO2,
which are early nonspecific warnings of increased interstitial
fluid in the lung.
Peak expiratory flow rate may decrease early after a massive
phosgene exposure. This nonspecific test helps to assess the
degree of airway damage and the effect of bronchodilator therapy.
Decreased lung compliance and carbon monoxide diffusing capacity
are particularly sensitive indicators of interstitial fluid
volume in the lung, but are complex tests for hospital use only.
Early findings on chest x-ray are hyperinflation followed
later by pulmonary edema without cardiovascular changes of
redistribution or cardiomegaly. V/Q scanning is very sensitive
but nonspecific and for hospital use only.
Terminate exposure as a vital first measure. This may
be accomplished by physically removing the casualty from the
contaminated environment or by isolating him from surrounding
contamination by supplying a properly fitting mask.
Decontamination of liquid agent on clothing or skin terminates
exposure from that source.
Execute the ABCs of resuscitation as required.
Establishing a patent airway is especially crucial in a patient
exhibiting hoarseness or stridor; such individuals may face
impending laryngeal spasm and require intubation. Establishing a
clear airway also aids in interpretation of auscultatory
findings. Steps to minimize the work of breathing must be taken.
Because of the always present danger of hypotension induced by
pulmonary edema or by positive airway pressure, accurate
determination of the casualty's circulatory status is vital not
just initially but also at regularly repeated intervals and
whenever indicated by the clinical situation.
Enforce rest. Even minimal physical exertion may
shorten the clinical latent period and increase the severity of
respiratory symptoms and signs in an organohalide casualty, and
physical activity in a symptomatic patient may precipitate acute
clinical deterioration and even death. Strict limitation of
activity (i.e., forced bed rest) and litter evacuation are
mandatory for patients suspected of having inhaled any of the
edemagenic agents. This is true whether or not the patient has
respiratory symptoms and whether or not objective evidence of
pulmonary edema is present.
Prepare to manage airway secretions and prevent/treat
bronchospasm. Unless superinfection is present, secretions
present in the airways of phosgene casualties are usually copious
and watery; they may serve as an index to the degree of pulmonary
edema and do not require specific therapy apart from suctioning
and drainage. Antibiotics should be reserved for those patients
with an infectious process documented by sputum gram staining and
culture. Bronchospasm may occur in individuals with reactive
airways, and these patients should receive theophylline, or
$-adrenergic bronchodilators. Steroid therapy is also indicated
for bronchospasm as long as parenteral administration is chosen
over topical therapy, which may result in inadequate distribution
to damaged airways. Methylprednisolone 700-1000 mg or its
equivalent may be given in divided doses (i.v.) during the first
day and then tapered during the duration of the clinical illness.
The increased susceptibility to bacterial infection during
steroid therapy mandates careful surveillance of the patient. No
human studies have shown any benefit from steroids, and steroids
are thus not recommended in individuals without evidence of overt
or latent reactive airway disease.
Prevent/treat pulmonary edema. Positive airway pressure provides some control over the clinical complications of pulmonary edema. Early use of a positive pressure mask may be beneficial. Positive airway pressure may exacerbate hypotension by decreasing thoracic venous
return, necessitating intravenous fluid administration and
perhaps judicious use of the pneumatic anti-shock garment.
Prevent/treat hypoxia. Oxygen therapy is definitely
indicated and may require supplemental positive airway pressure
administered via one of the several available devices for
generating intermittent or continuous positive pressure.
Intubation with or without ventilatory assistance may be
required, and positive pressure may need to be applied during at
least the end-expiratory phase of the ventilator cycle.
Prevent/treat hypotension. Sequestration of
plasma-derived fluid in the lungs may cause hypotension, which
may be exacerbated by positive airway pressure. Urgent
intravenous administration of either crystalloid or colloid
(which in this situation appear equally effective) may need to be
supplemented by the judicious application of the pneumatic
anti-shock garment. The use of vasopressors is a temporizing
measure until fluids can be replaced.
Patients seen within 12 hours of exposure: A patient with
pulmonary edema only is classified immediate if intensive
pulmonary care is immediately available. In general, a shorter
latent period portends a more serious illness. A delayed
patient is dyspneic without objective signs and should be
observed closely and retriaged hourly. An asymptomatic patient
with known exposure should be classified minimal and
observed and retriaged every two hours. If this patient remains
asymptomatic 24 hours after exposure, discharge the patient. If
exposure is doubtful and the patient remains asymptomatic 12
hours following putative exposure, consider discharge. An expectant
patient presents with pulmonary edema, cyanosis, and
hypotension. A casualty who presents with these signs within six
hours of exposure generally will not survive; a casualty with the
onset of these signs six hours or longer after exposure may
survive with immediate intensive medical care.
Patients seen more than 12 hours after exposure: A patient
with pulmonary edema is classified immediate providing he
will receive intensive care within several hours. If cyanosis and
hypotension are also present, triage the patient as expectant.
A delayed patient is dyspneic and should be observed
closely and retriaged every two hours. If the patient is
recovering, discharge him 24 hours after exposure. An
asymptomatic patient or patient with resolving dyspnea is
classified minimal. If the patient is asymptomatic 24
hours after exposure, discharge him. A patient with persistent
hypotension despite intensive medical care is expectant.
If the patient had only eye or upper airway irritation and is asymptomatic with normal physical examination 12 hours later, he may be returned to duty. If the patient's original complaint was dyspnea only, yet physical examination, chest x-ray, and arterial blood gases are all normal at 24 hours, he may be returned to duty. If the patient presented initially with symptoms and an abnormal physical examination, chest x-ray, or arterial blood gas, he requires close supervision, but can be returned to duty at 48 hours if physical examination, chest x-ray, and arterial blood gases are all normal at that time.