miosis in 43% of children exposed to OP pesticides, isolated CNS effects (stupor
and coma) in the absence of peripheral muscarinic effects, incidences of seizures
varying from 8% to 22%, and weakness and hypotonia (seen in 70% to 100% of
victims) often in the absence of glandular secretions. The clinician should be
prepared for subtle and sometimes significant differences in children from the
classic cholinergic toxidrome seen in adults.
Disposition and Prognosis. The disposition of exposed patients depends on
severity of symptoms and route of exposure. Most patients presenting after vapor
exposure manifest peak toxicity by the time of hospital arrival with only miosis,
which may persist for up to 6 weeks. These children may be discharged. After
dermal exposure, symptom onset may lag up to 18 hours, even after thorough
skin decontamination, and most experts recommend a 24-hour observation period
even for initially asymptomatic victims.
The prognosis for full recovery from even severe nerve-agent poisoning
appears to be good with timely life-support interventions and adequate antidotal
therapy. Apneic patients have recovered ventilatory function within 3 hours, and
once consciousness was regained, muscle weakness and obtundation have
resolved over a few days, whereas miosis and subtle mental status effects have
persisted for several weeks. Significant histologically demonstrable
neuropathologic changes in brain tissue persisting after acute exposures are
typically seen only in exposed individuals who exhibited seizure activity during
the acute cholinergic crisis. Nerve agents appear not to cause intermediate
syndrome (IMS), a syndrome of weakness, especially of cranial nerve–innervated
muscles (neck flexors and respiratory muscles) and limb muscles seen in
survivors of Sri Lankan suicide attempts involving OP insecticides. Two acutely
poisoned Japanese nerve-agent casualties, one from the Tokyo attack and one
from an earlier attack in Matsumoto, developed organophosphate-induced
delayed neurotoxicity, or OPIDN (also called organophosphate-induced delayed
polyneuropathy, or OPIDP), a delayed polyneuropathy resulting in long-term and
in some cases permanent upper motor neuron lesions with spasticity and
hyperreflexia. However, these are the only known cases associated with nerveagent exposure, and it is likely that extremely high exposures are necessary to

cause this delayed neuropathy. Exposure or suspected exposure to nerve agents
has also been associated with a syndrome that has been called chronic
organophosphate-induced neuropsychiatric disorders (COPIND) and, more
recently, organophosphorus ester–induced chronic neuropathy (OPICN), a
constellation of neurobehavioral and neurologic effects including defective


autonomic-nervous-system regulation, nightmares, headache, drowsiness,
dizziness, anxiety, apathy, confusion, restlessness, emotional lability, anorexia,
insomnia, lethargy, inability to concentrate, memory deficits, depression,
irritability, generalized weakness, and tremors as well as subtle
electroencephalographic changes. This syndrome can be difficult to differentiate
from posttraumatic stress disorder (PTSD) but appears to be distinct from it.

Vesicants
The major vesicants, or blistering agents, are cellular poisons and include the
mustards (sulfur mustards and nitrogen mustards) and Lewisite. The mustards act
primarily as alkylating and inflammatory agents, whereas Lewisite is an organic
arsenical believed to affect the thiol groups in critical cellular enzymes. Because
little clinical experience with Lewisite exposure exists, this discussion focuses on
mustard.
Mustard exists as an oily, yellow to dark brown liquid with a garlic, mustard, or
“hot asphalt” odor. It may vaporize at high temperatures, and mustard vapor,
unlike most other chemical vapors, can penetrate skin and lead to early tissue
damage and eventual blistering, thus warranting emergent skin decontamination.
Mustard forms a cyclic ethylsulfonium ion that is a potent alkylating agent
binding to DNA and other cellular constituents and causing injury to rapidly
reproducing cells with local effects most evident on the skin and in the eyes and
respiratory tract. With severe exposures, the bone marrow, GI mucosa, and the
CNS may also be damaged. Although mustard-induced cell injury begins within

the first few minutes after exposure, clinical effects of mustard usually follow a
latent period of up to 4 to 6 hours that is inversely related to dose. Skin lesions
after liquid contact begin with erythema, followed by blister formation; after large
doses there is skin sloughing without blister formation ( Fig. 132.8 ). The burns
are usually of partial thickness. A “string-of-pearls” distribution of blisters is
sometimes seen to surround a central area of normal-appearing skin; in truth, the
central area is too injured to form vesicles. Blister fluid does not contain active
mustard and is not hazardous.


FIGURE 132.8 A patient with mustard-induced skin blisters. (Reprinted with permission from
Greenberg MI. Greenberg’s Text-Atlas of Emergency Medicine . Philadelphia, PA: Lippincott
Williams & Wilkins; 2005:968.)

Vapor exposure results in later, and usually milder, skin injury. Ocular lesions
from vapor include conjunctival inflammation and corneal damage. Permanent
blindness is a rare complication, but many patients presenting for treatment may
be functionally blind from pain and blepharospasm. Vapor-induced pulmonary
effects begin, typically after a delay of 1 to several hours, with upper respiratory
tract irritation and may progress through dyspnea and a productive cough to a
severe necrotizing tracheobronchitis with pseudomembrane formation. Patients
may succumb to secondary bacterial bronchopneumonia. Bone marrow damage
may occur in severe cases on about the third to fifth day after exposure and
manifest as progressive pancytopenia. Leukocyte counts less than 500/mm3 or
precipitous decreases in the leukocyte count portend a serious risk of sepsis and
death.
Experience with children exposed to vesicants is limited. An accident
involving the explosion of a mustard-containing shell caused a heavy exposure to
three children. These patients presented acutely with altered mental status, and
two of them died 3 to 4 hours after exposure. A case series of Iranian children and

adolescents exposed to mustard during the Iraq–Iran War found that they
exhibited a shorter onset and more severe dermal lesions compared with adults.


Because mustard penetrates tissue rapidly and binds to cellular components
within the first 2 to 5 minutes, the most important early intervention is immediate
decontamination, ideally within the first 2 minutes. Decontamination after a half
hour is unlikely to affect the eventual development of local effects, but even late
removal of agent can stop continuing absorption and limit the total internal dose.
As with nerve agents, RSDL is particularly effective for skin decontamination. In
contrast, soap and water often ends up simply smearing agent and increasing the
area for absorption. No specific antidotes to mustard poisoning are available.
Supportive care for skin lesions is analogous to that provided for burn injury,
although fluid requirements are usually far less than with comparable thermal
burns. Additional treatment of respiratory tract inflammation, ocular injury, and
immunosuppression associated with leukopenia may be required (see Chapters 93
Hematologic Emergencies , 99 Pulmonary Emergencies , 123 Ophthalmic
Emergencies ) and bone marrow stimulating factors may be needed.

Pulmonary Agents
Toxic inhalant agents, including chlorine and phosgene, may cause injury in
several ways, including simple asphyxia by displacing oxygen, topical damage to
airways or alveoli, systemic absorption through the pulmonary capillary bed, and
allergic hypersensitivity reactions. Both chlorine and phosgene were used in
battle in World War I, are commonly used for industrial purposes today, and are
reviewed briefly in this section.
Chlorine is a dense, acrid, yellow-green gas with intermediate water solubility
and chemical reactivity, whereas phosgene has low solubility and reactivity.
Because the initial irritant symptoms of gas exposure tend to correlate directly
with water solubility and chemical reactivity, low-dose exposures to chlorine and

even moderate exposures to phosgene might cause either no symptoms at all or
only mild irritation of mucous membranes. Victims could easily dismiss these
effects, thus prolonging exposure and the severity of the ultimate lung injury.
Phosgene (carbonyl chloride) also generates hydrochloric acid, contributing
particularly to upper airway, nasal, and conjunctival irritation at higher doses.
Also generated is a carbonyl group that participates in acylation reactions at the
pulmonary alveolocapillary membranes; the resulting leakage of fluid across
damaged membranes eventually leads pathologically to pulmonary edema and
clinically to acute lung injury (ALI), including its most severe form, acute
respiratory distress syndrome (ARDS). Phosgene lung injury may also be
mediated in part by an inflammatory reaction associated with leukotriene
production.