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 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 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 to 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 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 to 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 to minutes, the most important early intervention is immediate decontamination, ideally within the first 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 ... 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