Chemical Terrorism Update: Vesicants

Chemical vesicants do harm that goes far more than skin deep, with effects ranging from vision loss to convulsions to hopeless respiratory failure.The authors discuss what to anticipate and how to care for a patient presenting with vesicant exposure.

By Manuel Armada, MD, and Moss Mendelson, MD

Dr. Armada is a third-year emergency medicine resident and Dr. Mendelson is an associate professor in the department of emergency medicine at Eastern Virginia medical School, Norfolk, Virginia.

 

What are the vesicant chemical agents?

Chemical agents in the vesicant category include sulfur mustard, nitrogen mustard, lewisite, and phosgene oxime. Vesicants are so named because exposure to these agents causes vesicles or blisters to form on the skin. Direct contact with these agents can also damage the eyes and respiratory system. The gastrointestinal system, central nervous system, and bone marrow are affected through systemic absorption.
 

What are the physical characteristics of the vesicants?

Mustard, the prototypical vesicant agent, is an oily liquid that comes in a variety of colors ranging from brown to yellow. Its odor may smell like garlic, onion, horseradish, or mustard itself. Mustard evaporates very slowly and tends to be a liquid hazard under most conditions. A vapor hazard occurs at temperatures above 100°F, influenced by other environmental conditions such as humidity. A lethal dose of liquid mustard can be as low as 100 mg/kg (about one teaspoon for an average adult).

Lewisite is an oily, odorless liquid. It is more volatile than mustard and smells like geraniums in its gaseous state. Unlike mustard, which has a time interval of hours between exposure and the onset of symptoms, lewisite causes immediate pain and irritation on contact. Like mustard, however, the lesions require hours to fully develop. The two agents have equivalent lethality.

Treatment for lewisite and mustard exposure is generally supportive. British anti-lewisite (BAL or dimercaprol) is considered a partial antidote for lewisite only and will alleviate some of its effects. (This is the same antidote currently being used as a heavy metal chelator.)

Phosgene oxime is more of an urticant, producing irritation without blisters, but it is still classified as a vesicant. It is a colorless solid or yellowish-brown liquid (at temperatures above 95°F) that may have a peppery or pungent odor. Phosgene oxime causes immediate pain and irritation on contact with the skin or mucous membranes.

Because very little information exists regarding the toxicity and mechanism of action of both lewisite and phosgene oxime and because the medical management for these two agents and mustard is similar, all three will be discussed as a group.
 

What is the mechanism of action of the vesicants?

Vesicant liquids and vapors penetrate most thin-layer fabrics. Once the vesicant reaches the skin, it slowly diffuses into aqueous solutions, such as sweat and extracellular fluid, and the lipophilic nature of the mixture ensures effective absorption, even through intact skin. The rapid penetration of vesicant agents is enhanced by moisture, heat, and thin skin, such as on the external genitalia, perineum, axillae, and neck.

As the vesicant penetrates the skin, approximately 10% becomes bound to intracellular and extracellular enzymes, proteins, DNA, RNA, and other cellular components. The rest of the dose can enter the circulation and spread systemically. Vesicant agents can affect all major organ systems, including the kidneys, liver, lungs, intestines, and brain. However, since the vesicant that reaches the bloodstream will be somewhat diluted, clinical effects on these organs are usually seen only with exposure to high doses.

Once bound, vesicants are thought to exert their biological damage via DNA alkylation and crosslinking in rapidly dividing cells, although the exact mechanism is not known. Damage to rapidly dividing cells, such as basal keratinocytes, mucosal epithelium, bone marrow precursor cells, and gastrointestinal cells, leads to cellular death and an inflammatory reaction. In the skin, protease digestion of anchoring filaments at the epidermal-dermal junction causes the blisters to form. Lastly, vesicants possess some mild cholinergic activity, causing miosis and gastrointestinal symptoms.

Vesicants are eliminated primarily by the renal system as a by-product of alkylation. They are considered to be mutagenic and carcinogenic, especially to the upper airway and skin. Because vesicants rapidly affix to tissue, wounds and drainage contain very little free vesicant and thus pose no contamination or health hazard to health care providers.
 

What are the clinical effects of vesicants?

Although vesicant agents cause cellular changes within minutes of contact, the onset of signs and symptoms may take hours. With mustard, onset is typically between four to eight hours, but it may be as long as 24 to 48 hours. The sooner signs and symptoms develop after exposure, the more likely the patient's morbidity will progress. Most deaths from vesicant exposure are caused by infection, related in part to a compromised immune system, usually culminating in pulmonary insufficiency on post-exposure days 5 through 10.

The organ most sensitive to vesicant agents is the eye, which can develop intense conjuctival and scleral pain, swelling, lacrimation, blepharospasm, photophobia, and miosis. Blisters do not form in the eye, but damage to the corneal epithelial cells leads to permanent vision loss. Higher vesicant concentrations can cause corneal edema, perforations, blindness, panophthalmitis, and scarring between the iris and lens. Most ocular signs and symptoms do not appear for an hour or more after exposure.

Skin exposure to vesicants causes a pruritic, erythematous rash within 4 to 8 hours, followed by blistering 2 to 18 hours later. The rash resembles a sunburn. Contact with vesicant vapor can result in partial-thickness burns; contact with vesicant liquid may also cause full-thickness burns. Small vesicles can develop within the erythematous areas, coalescing to form bullae. These bullae are large, dome-shaped, thin-walled, and translucent with a yellowish color. The fluid in the bullae is thin, clear, or straw-colored initially, but it will later turn yellow and coagulate.

Higher doses of vesicant exposure may cause lesions that develop central zones of coagulation necrosis with bullae in the periphery. Exposure that causes burns covering more then 25% of total body surface area is usually fatal.

The gastrointestinal mucosa is very sensitive to vesicant agent damage from both ingestion and systemic absorption. Ingestion can cause chemical burns to the gastrointestinal tract and cholinergic stimulation. The cholinergic effects usually cause nausea (with or without vomiting) and last 24 hours or less. However, nausea, vomiting, bloody diarrhea, and constipation can occur several days after severe exposure. Delayed gastrointestinal effects, which are uncommon, indicate a poor prognosis.

Respiratory damage from vesicant exposure is dose-dependent. It may be confined to the upper airways with mild to moderate exposure, but with severe exposure the lower airways may also be involved. Damage to the airways begins several hours after exposure and may progress over several days. Patients exposed to low doses of a vesicant may complain of nasal pain, rhinorrhea, epistaxis, sinus pain, laryngitis, productive cough, wheezing, and dyspnea. Higher doses cause necrosis of the respiratory epithelium and damage to the airway musculature, resulting in an inflammatory response that causes pseudomembrane formation and ultimately airway obstruction.

Although uncommon, fatal hemorrhagic pulmonary edema may result from severe vesicant exposure. The most common cause of death, however, is respiratory failure and its complications. Within the first 24 hours, mechanical obstruction from pseudomembrane formation and laryngospasm causes most deaths. Between days 3 and 6, most fatalities result from secondary bacterial infections caused by denuded respiratory mucosa and necrotic debris. Deaths that occur a week or more after exposure are usually the result of bone marrow suppression and sepsis.

Central nervous system exposure to small doses of a vesicant can cause the patient to become apathetic, lethargic, and ataxic. Higher doses can cause convulsions, hyperexcitability, insomnia, or coma. The etiology of these effects remains poorly understood. Also, it should be noted that case reports suggest that cognitive problems can persist for years after exposure.

Other clinical effects caused by systemic absorption of vesicants include infection, hemorrhage, anemia from bone marrow suppression, and hepatic toxicity. Loss of taste and smell, lung fibrosis, recurrent respiratory infections, asthmatic bronchitis, upper airway and dermatologic cancers, infertility, fetal abnormalities, and developmental defects have also been noted.
 

What is the diagnostic workup for vesicant-exposed patients?

There are several laboratory tests that may help with the evaluation of an exposed patient, but there is no test for measuring vesicant levels in the blood or tissues because of the rapid biotransformation and bonding that vesicants undergo within minutes of absorption. Specially equipped laboratories can measure the level of a urinary metabolite of vesicants called thiodiglycol, but the clinical utility of this test is marginal.

Patients often initially develop leukocytosis, the severity of which usually correlates with the degree of tissue injury. However, white blood cell counts can start to fall several days after exposure, indicating damage to bone marrow precursor cells. Pancytopenia can occur with severe exposure and usually indicates a lethal dose.

Vesicant agents severely impair airway and skin defense mechanisms, putting patients at risk for secondary bacterial infections. Glucose and serum electrolyte levels should be measured in all patients exposed to vesicants; chest x-ray, pulse oximetry, sputum cultures, and arterial blood gas analysis are also recommended for inhalation exposures. Lastly, examination of stool for occult blood will help identify gastrointestinal bleeding.
 

Are there any special decontamination procedures for vesicant exposure?

Mustard agent is rapidly absorbed through inhalation or contact with the skin. Patients whose skin or clothing is contaminated with mustard can contaminate first responders and other health care personnel through direct contact or vapors. All personnel must be trained and appropriately clothed before coming into contact with a patient who has not been decontaminated. It is recommended that respiratory and ocular protection include a pressure-demand, self-contained breathing apparatus or a chemical-protective, full-face mask with an activated charcoal canister. For skin protection, a chemical-protective overgarment, butyl rubber chemical-protective gloves, and boots should be worn.

Ideally, all patients should be decontaminated before transport to the hospital. However, if this is not possible, decontamination must take place in a facility capable of containing the contamination. All of the patient's clothing must be removed, and the patient must be showered with soap and warm water, using low water pressure to minimize penetration of the agent into the skin. If water is in short supply, decontamination can be achieved using 0.5% sodium hypochlorite solution or absorbent powders like flour, talcum powder, or Fuller's earth. The patient's clothing and personal belongings should then be sealed in a double bag for proper disposal.

Patients who went home, showered, and changed clothes before presenting at the hospital can be considered decontaminated. However, the patient's entire home should be considered contaminated and would require decontamination.
 

How should patients who have been exposed to vesicants be managed?

Decontamination within one to two minutes after vesicant exposure is the only effective way to minimize tissue damage. If decontamination occurs later than that, it is not likely to improve the victim's condition or prognosis, but it will protect personnel from contamination or exposure. There is no antidote for vesicant exposure, except for lewisite, and treatment consists of supportive therapy only.

Initial evaluation and treatment should always begin with airway, breathing, and circulation. Advanced cardiac life support protocols should be followed for any patient in cardiopulmonary compromise and advanced trauma life support protocols followed for any trauma patient. It is important to remember the latency of vesicant agents and the fact that a short time between exposure and the onset of signs and symptoms portends higher morbidity. Therefore, patients who present soon after exposure might not have any signs and symptoms. Nevertheless, they should be observed for at least six hours after exposure before being considered for discharge.

All ocular exposures should be treated with copious irrigation and a complete eye examination, including visual acuity and slit-lamp examination. Regular application of anticholinergic ophthalmic ointment will minimize synechiae formation; a topical antibiotic applied regularly will reduce the likelihood of infection. Initially, a topical analgesic may be used to help with examination and irrigation, but systemic analgesia is appropriate after the initial evaluation. A lubricating ointment applied to the eyelids regularly will help prevent adhesions and scarring during the healing process. Topical steroids have proven to be of little value, but they may reduce inflammation during the first day or two. Dark glasses will help with the discomfort associated with photophobia, but the eyes should never be covered with bandages.

Disposition of the patient depends on the severity of exposure. Mild signs and symptoms that develop more than six hours after exposure can be treated as described above. The patient can then be discharged home with instructions to return to the hospital if signs and symptoms worsen and with an ophthalmology follow-up in two or three days. Signs and symptoms that develop earlier or that indicate severe exposure require immediate consultation with an ophthalmologist and admission to the hospital.

Skin exposures are treated like any other burns, bearing in mind that fluid loss is not of the same magnitude as thermal burns. Therefore, standard formulas for fluid replacement in burn victims should not be used. Instead, the individual needs of the patient should guide fluid replacement. Small bullae of one to two centimeters should be left intact; larger bullae should be unroofed. Any small, denuded area should be irrigated three to four times a day with copious amounts of saline or another sterile solution; a whirlpool should be used for larger lesions. After irrigation, a topical antibiotic, such as silver sulfadiazine, should be applied liberally to cover the skin.

Erythema and pruritus of the skin should be treated with a soothing solution such as calamine and with an antipruritic and systemic analgesic as needed. Patients with limited erythema six hours after exposure can be treated as described above and discharged home with instructions to return to the hospital if the erythema worsens and to follow up with their primary physician in one to two weeks. Any patient with significant erythema, with or without blisters, or early signs and symptoms indicating severe exposure should be admitted. If the patient has large, partial- or full-thickness burns, transfer to a burn unit is indicated. Like any severe burn, vesicant-induced skin lesions may take several months to heal.

Signs and symptoms of upper airway irritation, such as sore throat, nonproductive cough, and hoarseness, may benefit from a cool-steam vaporizer, lozenges, or cough drops. Bronchospasm should be treated with bronchodilators and steroids should be considered. Patients with signs and symptoms of lower airway damage should be given oxygen-assisted ventilation, with bi-level positive airway pressure or continuous positive airway pressure, as necessary. If there is any laryngeal spasm or edema, the patient should be intubated before progressive tissue damage makes it difficult or impossible to do so. If pseudomembrane formation is suspected, then bronchoscopy should be performed to allow for direct visualization of the airways and for suctioning of debris.

It is common for patients to develop a sterile chemical pneumonitis several days after mustard exposure, with infiltrates visible on chest x-ray, leukocytosis, and fever. Differentiation from an infectious process is difficult. Antibiotics should not be given prophylactically, and aggressive attempts to isolate a causative organism should be made if infection is suspected. Infections usually develop on the third or fourth day after exposure.

Patients with mild upper airway symptoms presenting more than six hours after exposure can be treated as described above. They can then be discharged home with instructions to return to the hospital if their symptoms worsen and to follow up with their primary or pulmonary physician in one to two weeks for repeat chest x-rays. Patients who experience severe symptoms at any time after exposure should be admitted to the hospital. Any patient with damage to the lower airways presenting at any time after exposure should be admitted to the intensive care unit.

For ingestion, vomiting should not be induced. If the patient is alert with an intact gag reflex, four to eight ounces of milk or water can be given. To control nausea and vomiting, atropine or an antiemetic should be given. Activated charcoal has been shown to be of no benefit, but if a large dose of a vesicant agent has been ingested within 30 minutes, then orogastric lavage may be performed to remove the ingested material. Gastrointestinal contamination is uncommon; when it does occur, it usually requires admission to the hospital.

If bone marrow damage has occurred, the patient should be admitted to the oncology floor or burn unit for reverse isolation. Blood transfusions may be helpful. Granulocyte colony-stimulating factor and bone marrow transplants have been used successfully in animal experiments. Nonabsorbable antibiotics for sterilization of enteric organisms have been used to reduce the risk of sepsis.

Other treatments for vesicant exposure that have been investigated include hemodialysis and sodium thiosulfate. Sulfur donors, such as sodium thiosulfate, given to the patient intravenously within minutes of exposure, may prevent death. Hemodialysis, on the other hand, has not been effective and has actually been harmful in several patients.

Back to Index

Emerg Med 34(9):51, 2002

Printable version of this article

E-Mail this Article