Airways
Mustard produces dose-dependent damage to
the mucosa of the respiratory tract, beginning with the upper airways
and descending to the lower airways as the amount of mustard increases.
The inflammatory reaction varies from mild to severe, with necrosis of
the epithelium. When fully developed, the injury is characterized by an
acute inflammation of the upper and lower airways, with discharge in the
upper airway, inflammatory exudate, and pseudomembrane formation in the
tracheobronchial tree. The injury develops slowly, intensifying over a
period of days.
After a low-dose, single exposure,
casualties might notice a variety of catarrhal symptoms accompanied by a
dry cough; on examination, they might have pharyngeal and laryngeal
erythema. Hoarseness is almost always present, and the patient often
presents with a barking cough. Typically, this hoarseness may progress
to a toneless voice, which appears to be particularly characteristic of
mustard exposure. Patients characteristically note a sense of chest
oppression. All of these complaints typically commence approximately 4
to 6 hours after exposure, with sinus tenderness appearing hours later.
Vapor concentrations sufficient to cause these symptoms typically
produce reddened eyes, photophobia, lacrimation, and blepharospasm.
There may be loss of taste and smell. Patients occasionally experience
mild epistaxis and sore throat. In individuals with abnormal sensitivity
(smokers and patients with irritable airways or acute viral illness),
prominent wheezing and dyspnea may be present.58
Exposures to higher concentrations of
vapor result in an earlier onset and greater severity of the above
effects. Hoarseness rapidly progresses to aphonia. Severe tachypnea and
early radiological infiltrates may appear. More-intense respiratory
exposures create necrotic changes in the respiratory epithelium that
result in epithelial sloughing and pseudomembrane formation. There may
be substantial airway occlusion from the inflammatory debris or from
pseudomembranes, which can obstruct the upper airways as they form or
can break off and obstruct lower airways.16,58,60
The initial bronchitis is nonbacterial.
White blood cell elevation, fever, pulmonary infiltrates seen on
radiograph, and colored secretions may all be present to mimic the
changes of a bacterial process. This process is sterile during the first
3 to 4 days; bacterial superinfection occurs in about 4 to 6 days.
Careful assessment of the sputum by Gram’s stain and culture should be
done daily.60
 |
| Fig. 7-11. A surgically excised lung
from an Iranian mustard casualty showing bronchiectasis and
severe chronic infection. Reprinted with permission from Freitag
L, Firusian N, Stamatis G, Greschuchna D. The role of
bronchoscopy in pulmonary complications due to mustard gas
inhalation. Chest. 1991;100:1438. |
Mustard has little effect on lung
parenchyma. Its damage is confined to the airways and the tissue
immediately surrounding the airways, except after an overwhelming
exposure to mustard and as a terminal event.74 These changes
are most intense in the upper airways and decrease in the trachea,
bronchi, and smaller bronchioles—presumably reflecting a differential
disposition of vapor on the mucosal surface.71,75 Pulmonary
edema is not a feature; however, it may occur in the terminal stages.60,74
The lungs of animals exposed to mustard
show alternating areas of atelectasis and emphysema. Atelectasis is
thought to be caused by the clogging of bronchioles with mucus, and the
emphysema is compensatory.76 These findings were confirmed
when lungs resected at thoracotomy from Iranian casualties from the
Iran–Iraq War showed similar effects.77 As seen in Figure
7-11, the lungs showed bronchiectasis and severe chronic inflammation.
The bronchiectasis was due to full-thickness injury of the airways. In
some casualties, this injury healed by scarring of such intensity that
severe and unrelenting tracheobronchial stenosis developed.
Gastrointestinal Tract
Nausea and vomiting are common within the
first few hours after mustard exposure, beginning at about the time the
initial lesions become apparent. The early nausea and vomiting, which
are generally transient and not severe, may be caused by the cholinergic
activity of mustard,9,33 by a general reaction to injury, or
because of the unpleasant odor.33 Nausea and vomiting that
occur days later are probably due to the generalized cytotoxic activity
of mustard and damage to the mucosa of the gastrointestinal tract.
Diarrhea is not common, and
gastrointestinal bleeding seems to be even less common. Animals that
were given approximately 1 LD50 of mustard (administered
either intravenously or subcutaneously) had profuse diarrhea, which was
frequently bloody60,78; however, this was unusual when
mustard was administered percutaneously or by inhalation. (Diarrhea was
more common after nitrogen mustard.9)
Diarrhea and gastrointestinal bleeding do
not seem to be common in humans. Of 107 autopsied cases, none had
experienced diarrhea; and in the 57 cases in which the gastrointestinal
tract was thoroughly examined, none had significant lesions.75
In several reported series of Iranian casualties, totaling about 700
casualties, few had diarrhea and only a very few who died had bloody
diarrhea.16,62,79 Constipation was noted in casualties with
mild exposure.60
Central Nervous System
Although the effects are not usually
prominent clinically, mustard affects the CNS. Reports of World War I
casualties described apathy, depression, intellectual dullness, and
languor.60 Of 233 Iranian casualties sent to various western
European hospitals for medical care during the Iran–Iraq War, about
83% had CNS complaints; most complaints, however, were mild and
nonspecific.62
Large amounts of mustard administered to
animals (via the inhalational, intravenous, subcutaneous, or
intramuscular routes) caused hyperexcitability, abnormal muscular
movements, convulsions, and other neurological manifestations.60,80
Animals died a “neurological death” a few hours after receiving a
lethal amount of mustard.9 Autopsies of these animals
disclosed few abnormalities.80
After three children were accidentally
exposed to a large amount of mustard, two of them presented with
abnormal muscular activity, and the third alternated between coma and
agitation. The first two children died 3 to 4 hours after exposure,
possibly from neurological mechanisms.22 Whether these CNS
manifestations are from a cholinergic activity of mustard or from other
mechanisms is unknown.
Death
Most casualties die of massive pulmonary
damage complicated by infection (bronchopneumonia) and sepsis (resulting
from loss of the immune mechanism). When exposure is not by inhalation,
the mechanism of death is less clear. In studies with animals in which
mustard was administered via routes other than inhalational, the animals
died from 3 to 7 days after the exposure; they had no signs of pulmonary
damage and often had no signs of sepsis. The mechanism of death was not
clear, but autopsy findings resembled those seen after radiation.81
(Mustard is considered to be a radio-mimetic because it causes tissue
damage similar to that seen after radiation.)
Diagnosis
The differential diagnosis of mustard
casualties on the battlefield after a known chemical attack is not
difficult. The history of a chemical attack is useful, particularly if
the chemical agent is known. Simply questioning the casualty about when
the pain started—whether it started immediately after the exposure or
hours later—is very helpful. Whereas pain from Lewisite (the other
vesicant that causes blistering) begins seconds to minutes after
exposure, pain from mustard does not begin until the lesion develops
hours later.
Blisters appearing simultaneously in a
large number of people, in the absence of a known chemical attack,
should alert medical personnel to search the area with a chemical agent
detector. Because naturally occurring organisms, both plants and
insects, cause similar blisters, the appearance of one or more blisters
in only a single individual makes exposure to a natural substance the
more likely possibility.
Laboratory Tests
There is no specific laboratory test for
mustard exposure. As inflammation and infection occur, signs of these
(eg, fever and leukocytosis) will develop. Several investigational
studies have demonstrated the presence of significant amounts of
thiodiglycol, a major metabolite of mustard, in the urine of mustard
casualties. In two studies,82,83 Iranian casualties had
higher amounts of thiodiglycol in their urine than did control subjects.
In a third study, the urinary thiodiglycol secreted by a laboratory
worker accidentally exposed to mustard was quantitatively measured for a
2-week period (his postrecovery urine was used as a control); the
half-life of thiodiglycol was 1.18 days.23 The procedure for
analysis of thiodiglycol is described in Technical Bulletin Medical 296.84
Patient Management
Decontamination within 1 or 2 minutes
after exposure is the only effective means of preventing or decreasing
tissue damage from mustard. This decontamination is not done by
medical personnel. It must be performed by the soldier himself
immediately after the exposure. Generally, a soldier will not seek
medical help until the lesions develop, hours later. By that time, skin
decontamination will not help the soldier because mustard fixes to the
skin within minutes, and tissue damage will already have occurred.64
If any mustard remains on the skin, late
decontamination will prevent its spreading to other areas of the skin;
but after several hours, spreading will probably already have occurred.
Decontamination will, however, prevent mustard from spreading to
personnel who handle the casualty.
By the time a skin lesion has developed,
most of the mustard will already have been absorbed (and the chemical
agent will have fixed to tissue); and, unless the site was occluded, the
remaining unabsorbed agent will have evaporated. Mustard droplets
disappear from the surface of the eye very quickly, so late flushing of
the eye will be of no benefit, either.
However, all chemical agent casualties
must be thoroughly decontaminated before they enter a clean MTF. This
should be done with the realization that by the time a contaminated
soldier reaches an MTF, this decontamination will rarely help the
casualty; it does, however, prevent exposure of medical personnel.
Mustard casualties generally fall into
three categories. The first is the return to duty category. These
individuals have a small area of erythema or one or more small blisters
on noncritical areas of their skin; eye irritation or mild
conjunctivitis; and/or late-onset, mild upper respiratory symptoms such
as hoarseness or throat irritation and a hacking cough. If these
casualties are seen long after exposure, so that there is good reason to
believe that the lesion will not progress significantly, they can be
given symptomatic therapy and returned to duty.
The second category includes casualties
who appear to have non–life-threatening injuries but who are unable to
return to duty. Casualties with the following conditions must be
hospitalized for further care:
- a large area of erythema (with or without blisters),
- an extremely painful eye lesion or an eye lesion that hinders
vision, and
- a respiratory injury with moderate symptoms that include a
productive cough and dyspnea.
Some of these conditions may develop into life-threatening injuries, and
these categories, therefore, should be used only to assess a
casualty’s presenting condition. For example, an area of
erythema caused by liquid mustard that covers 50% or more of the body
surface area suggests that the individual was exposed to 2 LD50
of the agent. Likewise, dyspnea occurring within 4 to 6 hours after the
exposure suggests inhalation of a lethal amount of mustard.
The third category comprises those
casualties who appear to have life-threatening injuries when they first
present at an MTF. Life-threatening injuries include large skin burns
caused by liquid mustard, and early onset of moderate-to-severe
pulmonary symptoms. Most of the casualties in this category will die
from their injuries.
Many mustard casualties will fall into the
first category, the majority will fall into the second category, and
only a very small percentage of casualties will fall into the third
category. Data from World War I, in which only 3% of mustard injuries
were lethal despite the unsophisticated medical care at that time (eg,
no antibiotics), suggest that most mustard casualties are not severely
injured and that most of them will survive.
Most casualties of mustard exposure will,
however, require some form of medical care—from a few days to many
weeks. Eye care and airway care will promote healing within weeks; skin
lesions take the longest to heal and may necessitate hospitalization for
months.16 Casualties with mild-to-moderate mustard damage
will need supportive care. Pain control is extremely important. Fluids
and electrolytes should be carefully monitored. Although there is not a
great deal of fluid loss from mustard burns (compared with thermal
burns), a casualty will probably be dehydrated when he enters the MTF;
and a sick patient usually does not eat or drink enough. Parenteral
fluid supplements and vitamins may be of benefit. Casualties who have
lost their eyesight because of mustard exposure should be reassured that
they will recover their vision.
Casualties who do become critically ill
from their exposure to mustard will present with large areas of burns,
major pulmonary damage, and immunosuppression. Some of the casualties
may die from sepsis or from overwhelming damage to the airways and
lungs. Medical officers should remember, however, that even with the
limited medical care available in World War I, very few deaths were
caused by mustard exposure.
Despite the attention given to mustard
since World War I, research has not produced an antidote. Because
casualties have been managed in different eras and, more recently, in
different medical centers, there have been no standard methods of
casualty management, nor have there been any controlled studies of one
method compared to another. The following advice describes care by organ
system. Most casualties will have more than one system involved, and
many of these casualties will be dehydrated and have other injuries as
well.
Skin
The general principles for managing a
mustard skin lesion are to keep the casualty comfortable, keep the
lesion clean, and prevent infection. The burning and itching associated
with erythema can be relieved by calamine or another soothing lotion or
cream such as 0.25% camphor and menthol. These lesions should heal
without complication.
Small blisters (< 1 cm) should be left
alone; however, the surrounding area should be cleaned (irrigated) at
least once daily. An application of a topical antibiotic should
immediately be applied to the blisters and the surrounding area. The
blisters and the surrounding area do not need to be bandaged unless the
casualty will be returning to duty.
Larger blisters (> 1 cm) should be
unroofed and the underlying area should be irrigated (2 to 4 times
daily) with saline, sterile water, or clean soapy water, and liberally
covered (to a depth of 1 mm) with a topical antibiotic cream or ointment
(silver sulfadiazine, mafenide acetate, bacitracin, or Neosporin
[Burroughs Wellcome Co., Research Triangle Park, N. C.]). Dakin’s
solution (hypochlorite) was used on patients in World War I60
and during the Iran–Iraq War16 as an irrigating solution.
It does not detoxify the chemical agent in the skin, as was once
thought; however, it is an adequate antiseptic and keeps the area clean.
Multiple or large areas of vesication necessitate hospitalization for
frequent and careful cleaning; a whirlpool bath is a useful means of
irrigation. In general, care of mustard skin lesions is the same as that
of second-degree thermal burns, although the pathophysiology is
different.
Systemic analgesics should be given
liberally, particularly before manipulation of the burned area. Systemic
antipruritics (eg, trimeprazine) may be useful. Fluid balance and
electrolytes should be monitored. Fluids are lost into the edematous
areas, but fluid replacement is of less magnitude than that required for
thermal burns. Medical personnel accustomed to treating patients with
thermal burns must resist the temptation to overhydrate mustard burn
patients, which could lead to untoward consequences such as pulmonary
edema.16
Skin healing can take weeks to months but
usually is complete, although pigment changes may persist. Scarring is
proportional to the depth of the burn. Skin grafting is rarely needed,
but it was successful in one person who had a deep burn.25
Eyes
The basic principles of eye care are to
prevent infection and to prevent scarring. Although it is unlikely that
mustard will still be in the eye by the time the casualty is seen, the
eye should be irrigated to remove any possible chemical agent that might
be on the lashes and to remove any inflammatory debris that might be on
the surface of the eye. Mild lesions (eg, conjunctivitis) can be treated
three to four times daily with a soothing eye solution.
Casualties with more-severe eye lesions
should be hospitalized. Care for these patients should consist of at
least one daily irrigation, preferably more, to remove inflammatory
debris; administration of a topical antibiotic three to four times
daily; and administration of a topical mydriatic (atropine or
homatropine) as needed to keep the pupil dilated (to prevent later
synechiae formation). Vaseline or a similar material should be applied
to the lid edges to prevent them from adhering to each other; this
reduces later scarring and also keeps a path open for possible infection
to drain. (When animals’ eyes were kept tightly shut, a small
infection could not drain, and a panophthalmitis developed that
completely destroyed the eyes.65)
Topical analgesics may be used for the
initial examination; however, they should not be used routinely as they
might cause corneal damage. Pain should be controlled with systemic
analgesics. The benefit of topical steroids is unknown; however, some
ophthalmologists feel that topical steroids may be helpful if used
within the first 48 hours after the exposure (but not after that). In
any case, an ophthalmologist should be consulted as early as possible on
this and other questions of care. Keeping the casualty in a dim room or
providing sunglasses will reduce the discomfort from photophobia.
The transient loss of vision is usually
the result of edema of the lids and other structures and not due to
corneal damage. Medical personnel should assure the patient that vision
will return. Recovery may be within days for milder injuries, while
those with severe damage will take approximately a month or longer to
recover.
Airways
The therapeutic goal in a casualty with
mild airway effects (eg, irritation of the throat, nonproductive cough)
is to keep him comfortable. In a casualty with severe effects, the goal
is to maintain adequate oxygenation. Antitussives and demulcents are
helpful for persistent, severe, nonproductive cough. Steam inhalation
might also be useful.
Hypoxia is generally secondary to the
abnormalities in the ventilation–perfusion ratio caused by toxic
bronchitis. Mucosal sloughing further complicates this abnormality.
Underlying irritable airways disease (hyperreactive airways) is easily
triggered; consequently, therapy with bronchodilators may be necessary.
Casualties with hyperreactive airways may benefit from steroid treatment
with careful attention to the added risk of superinfection. Oxygen
supplementation may be necessary for prolonged periods; this will
depend, primarily, on the intensity of mustard exposure and the presence
of any underlying pulmonary disorder.
Hypercarbia may result from a previously
unrecognized hyperreactive airways state or from abnormal central
sensitivity to carbon dioxide, complicated by increased work of
respiration (this state may result from bronchospasm). Bronchodilators
are acceptable initial therapy. Ventilatory support may be necessary to
assist adequate carbon dioxide clearance. The use of certain antibiotic
skin creams (such as mafenide acetate) to treat skin lesions may
complicate the acid–base status of the individual by inducing a
metabolic acidosis. Steroids should be considered if a prior history of
asthma or hyperreactive airways disease is obtained.
Initially, the bronchitis resulting from
mustard exposure is nonbacterial. White blood cell elevation, fever,
pulmonary infiltrates on a chest radiograph, and colored sputum may all
be present; however, careful assessment of sputum by Gram’s stain and
culture demonstrates that bacterial superinfection typically is not
present during the first 3 to 4 days. Antibiotic therapy should be
withheld until the identity of a specific organism becomes available. Of
particular importance is the patient’s immune status, which may be
compromised by a progressive leukopenia beginning about day 4 or 5. The
development of leukopenia signals severe immune system dysfunction;
massive medical support may become necessary for these patients. In
these instances, sepsis typically supervenes, and despite combination
antibiotic therapy, death commonly occurs.
A casualty with severe pulmonary signs
should be intubated early, before laryngeal spasm makes it difficult or
impossible. Intubation assists in ventilation and also allows suction of
necrotic and inflammatory debris. Bronchoscopy may be necessary to
remove intact pseudomembranes or fragments of pseudomembranes; one of
the Iranian casualties treated in western European hospitals during the
Iran–Iraq War died of tracheal obstruction by a pseudomembrane. Early
use of positive end-expiratory pressure or continuous positive airway
pressure may be beneficial. The need for continuous ventilatory support
suggests a bad prognosis; of the Iranian casualties treated in western
European hospitals who needed assisted ventilation, 87% died.16
An especially devastating pulmonary
complication, severe and progressive stenosis of the tracheo-bronchial
tree (Figure 7-12), was found in about 10% of the Iranian casualties
treated in western European hospitals during the Iran–Iraq War. This
complication was not recognized in World War I mustard casualties
because the degree of exposure required to cause severe tracheobronchial
injury resulted in early death from pneumonia: we must remember the
primitive nature of early 20th-century medicine and its lack of
antibiotics. With the Iranian casualties, bronchoscopy was of value when
used both for diagnosis and for therapeutic dilation.77
However, given the progressive nature of the scarring, unnaturally early
death from respiratory failure is to be expected in all such casualties.
a  |
 c |
b  |
Fig. 7-12. (a) Bronchoscopic
view of the trachea in an Iranian casualty 3 weeks after
exposure to mustard. Severe hemorrhagic bronchitis, mucosal
necrosis, and early scarring are apparent. (b)
Bronchogram from an Iranian casualty 1 year after his exposure
to mustard. The tip of a 10-mm rigid bronchoscope can be seen at
the upper margin of the figure. Severe generalized narrowing of
the entire tracheobronchial tree is apparent. The casualty
presented with dyspnea, cough, hypoxia, and hypercarbia. (c)
Bronchoscopic appearance of the carina of an Iranian casualty
who had been exposed to mustard several years before. There is
nearly total occlusion of the left main-stem bronchus. Reprinted
with permission from Freitag L, Firusian N, Stamatis G,
Greschuchna D. The role of bronchoscopy in pulmonary
complications due to mustard gas inhalation. Chest.
1991;100:1437–1438. |
Gastrointestinal Tract
The initial nausea and vomiting are rarely
severe and can usually be relieved with atropine or common antiemetics.
Later vomiting and diarrhea are usually indicative of systemic
cytotoxicity and require fluid replacement. |
b
c
b
b
d
b
b
d
