Disposition

Peak toxic effects occur within minutes to hours and resolve within 1 day. Observe asymptomatic patients exposed to nerve agent liquid for a minimum of 18 hours, since delayed onset of signs and symptoms have been reported (up to 18 h postexposure). Admit symptomatic patients with liquid exposure and monitor them for at least 1 day.

Cholinesterase levels alone should not guide disposition. Some sources recommend observation of asymptomatic patients exposed to nerve gas vapor for 1 hour. In reality, patients who present after inhaling nerve agent vapor have experienced peak effects long before arriving at the hospital, and no further absorption or worsening is expected. When patients experience no signs or symptoms other than eye findings, they may

Mechanism of action

Sulfur mustard (2,2,-dichlordiethyl sulfide) has been used as a chemical weapon since World War I. Nitrogen mustard, a derivative of sulfur mustard, was one of the first chemotherapy agents but never has been used in warfare. These vesicating agents cause blistering of exposed surfaces. Both mustard agents rapidly penetrate cells and generate a highly toxic intermediate episulfonium ion, which irreversibly alkylates DNA, RNA, and protein. This disrupts cell function and causes cell death. The chemical reaction is both temperature dependent and facilitated by the presence of water, which explains why warm, moist tissues are affected more severely. Actively reproducing cells, such as epithelial and hematopoietic cells, are most vulnerable to alkylation. Mustards also produce cytotoxicity by binding to and depleting cellular glutathione, a free radical scavenger. Glutathione depletion leads to the inactivation of sulfhydryl-containing enzymes, loss of calcium
homeostasis, lipid peroxidation, cellular membrane breakdown, and cell death.

Physical Properties

Mustards are oily liquids with odors of mustard, onion, garlic, or horseradish. Highly soluble in oils, fats, and organic solvents, mustards quickly penetrate skin and most materials, including rubber and most textiles. Sulfur mustard is considered a persistent agent with low volatility at cool temperatures but becomes a major vapor hazard at high ambient temperatures. Exposure to mustard vapor, not mustard liquid, is the primary medical concern. More than 80% of mustard casualties in World War I were caused by exposure to mustard vapor. Mustard vapor is 3 times more toxic than a similar concentration of cyanide gas; however, mustard liquid is also quite toxic. Skin exposure to as little as 1-1.5 tsp of liquid (7 g) is lethal to 50% of adults.

Clinical Effects

Mustards injure the skin, eyes, respiratory tract, GI mucosa, and hematopoietic system. The pattern of toxicity depends partly on whether the person is exposed to liquid or vapor. Liquid exposure primarily damages the skin, producing an initial erythema followed by blistering similar to a partial-thickness burn. Vapor exposure preferentially damages the upper respiratory tract (skin usually is not affected). Mustards penetrate cells and alkylate intracellular components in less than 2 minutes, yet signs and symptoms usually are delayed 4-6 hours (range, 1-24 h). The latent period is shorter with high-concentration exposures, such as those occurring at increased ambient temperature and humidity.

Skin

Chemical burns secondary to mustard often appear deceptively superficial on initial presentation. Earliest symptoms are pruritus, burning, and stinging pain over exposed areas. Moist, thinner skin is affected more severely. Affected areas appear erythematous and edematous. If contamination is more extensive, superficial bullae occur within 24 hours of exposure. Most burns are partial thickness, but full-thickness burns with deep bullae and ulcers may result from exposure to higher concentrations. Severe exposures clinically and histologically may resemble scalded skin syndrome or toxic epidermal necrolysis. Blister fluid does not contain active mustard and is not toxic.

Eyes

Eyes are especially sensitive to the effects of mustard. Ocular symptoms begin 4-8 hours postexposure. Earliest symptoms include burning pain, foreign body sensation, photophobia, tearing, and visual blurring. Clinical manifestations include eyelid edema, conjunctival injection and edema, chemosis, iritis, corneal abrasions, edema and ulceration, and decreased visual acuity. Permanent corneal scarring and blindness may occur with severe exposures.

Respiratory tract

Mustards primarily damage upper airway mucosa. Inhalation of mustard vapor produces a direct inflammatory effect on the respiratory tract, with damage occurring in a progressive downward pattern. The lower respiratory tract and lung parenchyma rarely are affected. Following a variable latent period of 2-24 hours, injury is characterized by hemorrhagic inflammation and airway erosion.

Upper respiratory tract is affected first, evidenced by sinusitis, sinus congestion, sore throat, and hoarseness. Lower respiratory tract symptoms include cough, dyspnea, and respiratory distress. Direct necrotic effect of mustard on airway mucosa produces epithelial sloughing and pseudomembrane formation, causing small and large airway obstruction.

In severe cases, late pulmonary sequelae include bronchopneumonia and bronchial obstruction. Pulmonary edema rarely occurs, because mustard rarely affects the lung parenchyma and alveoli. Patients with extensive mucosal involvement may suffer fatal respiratory compromise as late as several days after exposure.

Gastrointestinal tract

Mustard damages rapidly proliferating cells of the intestinal mucosa. GI involvement results in abdominal pain, nausea, vomiting, diarrhea, and weight loss.

Hematopoietic system

Mustards cause unpredictable bone marrow suppression, as leukocyte precursors begin dying 3-5 days after exposure. A leukopenic nadir usually occurs in 3-14 days, depending on the severity of exposure. Anemia and thrombocytopenia are late findings. Complete bone marrow aplasia has been reported.

Laboratory Tests

Diagnosis of mustard exposure is clinical. No laboratory tests identify or characterize acute exposure

Personal protective equipment

Liquid mustard contamination poses a dermal contact risk for emergency care personnel. Specialized protective military garments containing a charcoal layer to absorb penetrating sulfur mustard provide protection for up to 6 hours. These protective garments (chemical protective overgarment, battle dress overgarment, mission-oriented protective posture) are not available outside the military. Level A PPE provides the best protection for civilian first responders, and hospital-based emergency care personnel involved in subsequent decontamination should wear level A PPE.

Decontamination

Decontamination within 2 minutes of exposure is the most important intervention for patients with dermal exposure, since mustard rapidly becomes fixed to tissues, and its effects are irreversible. The classic description is an initial lack of signs and symptoms, which does not lessen the urgency to decontaminate patients as soon as possible.

Remove clothing immediately and wash the underlying skin with soap and water. Ocular exposure requires immediate copious irrigation with saline or water. Next, decontaminate the skin with 0.5% hypochlorite solution or with alkaline soap and water, which chemically inactivates sulfur mustard. Because mustard is relatively insoluble in water, water alone has limited value as a decontaminant. Decontamination after the first few minutes of exposure does not prevent subsequent damage but at least protects emergency care personnel from further contact exposure.

Supportive care

Treatment of mustard exposure proceeds according to symptoms. Since the effects of mustards typically are delayed, persons with complaints immediately after exposure may have an additional injury. Patients with signs of upper airway obstruction require endotracheal intubation or the creation of a surgical airway. Also consider endotracheal intubation for persons with severe exposures. Use the largest endotracheal tube that can pass through, since sloughing epithelium may obstruct smaller tubes. Have patients inhale moist air. Mucolytics also are recommended for those with respiratory complaints.

Avoid overhydration, since fluid losses generally are less than with thermal burns. Monitor fluid and electrolyte status and replace losses accordingly. Mustard-induced burns are especially painful, warranting the liberal use of narcotic analgesia. Adequate burn care is essential, since skin lesions heal slowly and are prone to infection. Severe burns may require debridement, irrigation, and topical antibiotics, such as silver sulfadiazine. Address tetanus toxoid immunity.

Severe ocular burns require ophthalmologic consultation. Eye care typically includes daily irrigation, topical antibiotic solutions, topical corticosteroids, and mydriatics. Treat minor corneal injuries similarly to corneal abrasions. Apply petroleum jelly to prevent eyelid margins from sticking together. More severe corneal injuries may take as long as 2-3 months to heal. Permanent visual defects are rare.

Specific therapy

Although no antidotes currently are available to treat mustard toxicity, several agents are under investigation, including antioxidants (vitamin E), anti-inflammatory drugs (corticosteroids), mustard scavengers (glutathione, N-acetylcysteine), and nitric oxide synthase inhibitors (L-nitroarginine methyl ester).

Administer granulocyte colony-stimulating factor to patients with bone marrow suppression following mustard exposure.

Disposition

Patients with significant respiratory tract burns usually require ICU admission and aggressive pulmonary care. Admit patients with significant dermal burns to a burn unit for aggressive wound management, analgesia, and supportive care. Arrange to monitor blood cell counts for 2 weeks following significant exposures. For 12 hours prior to discharge, observe patients who are initially asymptomatic following mustard exposure.

Most patients recover completely. Only a small fraction have chronic ocular or pulmonary damage. Approximately 2% of those exposed to sulfur mustard in World War I died, mostly due to burns, respiratory tract damage, and bone

Date: 2015-01-12; view: 599