VESICANT OR BLISTER AGENTS

Background

Blister agents were developed and used during the First World War as chemical warfare agents.48,49 These agents can be used in multiple forms to include liquid, solid or gas. Blister agents are generally broken down into sulfur mustard, nitrogen mustard, and Lewisite. Although used in different concentrations and in different forms, currently sulfur mustard is the most common blister agent used on the battlefield.

Sulfur mustard has three different main forms: HD, which is a distilled product and is close to 100% pure; H, which is undistilled sulfur mustard; and HT which is a mixture of HD and T (a thickener which can be added to sulfur mustard). HD or pure mustard is clear and smells of garlic. H sulfur mustard can be clear, yellow, red brown or black depending on the chemical mixture. In recent conflicts, to include the conflict with ISIS, H sulfur mustard is the chemical seen on the battlefield. This substance, made in crude chemistry labs, is a thick oily black substance which degrades quickly, only lasting 2-3 weeks in storage before degrading beyond utility.

Nitrogen mustard is much less commonly used as a chemical warfare agent. It is separated into 3 forms: N1, N2, and N3. Nitrogen mustard can have different smells with N1 smelling more like fish, N2 like fruit, and N3 like bitter almonds. Nitrogen mustards are clear to yellow oily substances that evaporate slowly and can harm first responders by contact or off-gassing from injured victims. Used for medicinal purposes such as chemotherapy or wart removal, these agents have so far never been used on the battlefield.

Lewisite is the last vesicant in this family of chemical agents. Related to arsenic, Lewisite is a clear liquid in pure form and amber or black in impure forms. Like the other vesicants, it is extremely irritating to the skin, eyes and respiratory tract. Lewisite can be mixed with HD for a more potent chemical warfare agent with properties from both substances. Unlike the other vesicants, Lewisite is the only vesicant that has an antidote to counter its systemic effects.

Signs and Symptoms of Vesicant or Blister Agents

The most common route of exposure of all blister agents is via the skin. Sulfur mustard agents will cause chemical burns associated with blisters within a few hours of contact with the skin or mucous membranes. Effects are not seen immediately on contact, but sulfur mustard is absorbed within minutes of contact on the skin or eye membranes. Second and third degree burns develop over 2-10 hours to the eyes and skin, causing intense pain, corneal perforations, erosions of the eyes, and blistering of all exposed skin. HD had a 2-3% mortality rate during WWI, but burns in excess of 25% body surface can be fatal. Nitrogen mustard has similar effects on the skin and eyes as sulfur mustard. However, Lewisite has immediate effects on the skin and eyes causing immediate pain and irritation and blistering much sooner than HD or nitrogen mustard.

Inhalation or ingestion of these vesicants causes similar problems, damaging the mucosa of both the respiratory and digestive systems, causing severe burns. Liquid agents, which are more concentrated, cause more severe damage than vapors which might be inhaled. Much like skin and eye exposure, inhalation of HD has a delayed effect on the respiratory tract, causing wheezing and swelling of the bronchioles several hours after exposure. As with skin symptoms, Lewisite causes respiratory symptoms much faster, usually within seconds to minutes, which then rapidly progresses to pulmonary edema following exposure.

Several late effects can occur from all blistering agents depending on the dose and the route of exposure of the agent. Bone marrow suppression can occur with increased likelihood of infection, and nitrogen mustard will cause anemia. High doses of sulfur mustard can cause convulsions and hyper-excitability. High doses of Lewisite can lead to hepatic necrosis, acute renal failure, and shock via capillary leaking, referred to as “Lewisite Shock.” There are many long-term effects suspected such as malignancies, corneal scarring, chronic respiratory disease, and dermal scarring.

Decontamination of Vesicant or Blister Agents

Safety of the rescuers and healthcare providers is the most important initial step when handling mustard casualties. First responders should have respiratory and skin protection during initial treatment of mustard casualties. Butyl rubber is the recommended level of protection for the hands; however, double layers of nitrile gloves will protect against exposure as well. Remember, contaminated patients may appear innocuous due to delayed onset of symptoms, however providers can still be exposed to significant injury to the lungs, eyes, and skin if not properly protected. The casualty must be decontaminated and all clothing and equipment removed; vesicants enter the body within minutes, but can stay on equipment or clothing for days after exposure.

Removal of the agent must occur within three to five minutes in order to reduce absorption. Removal with a dry cloth is the first step to clear the chemical from the skin, followed by RSDL. There is no antidote for vesicants like there is for nerve agents, so initial treatment is focused on rapid decontamination. Exposure to the eye causes faster absorption than skin and should be washed out immediately with water in order to minimize the effects. Eye wash kits with Morgan Lens can facilitate eye decontamination. It is important not to induce vomiting if there is any concern for ingestion, and activated charcoal has not been shown to be effective in these situations. After decontamination, standard burn care treatment is recommended for all dermal injuries. Fluid replacement may not follow the thermal burn estimates; however, urine output remains a good marker of adequate resuscitation and fluids should be titrated to target a urine output of 30-50 ml/hour.

Wounds which are chemically contaminated should be aggressively flushed and treated as if there is heavy contamination. Mustard enters the body systemically almost immediately after exposure to open wounds or mucus membranes. After initial decontamination, the patient should be transported to a hospital and observed for both systemic and local effects of the contaminated wound. Surgical debridement of open wounds will almost always be required for contaminated wounds.

Vesicant or Blister Agents Diagnostics

There is no readily available test to confirm vesicant exposure. Leukocytosis is anticipated on the first day and will rise with the amount of associated injury. Subsequently, bone marrow suppression occurs and leukocyte count will fall around day 3 to 5 with a nadir seen around day 9. Counts less than 500 indicate a poor prognosis. Chest X-ray can be used to monitor for pneumonitis, which typical appears in the first 2 to 3 days.

Treatment of Vesicant or Blister Agents

For asymptomatic patients exposed to sulfur mustard and nitrogen mustard, the effects may be delayed for skin, eye, and lungs; therefore, observation of potential exposures for 6-10 hours is recommended.

Patients with eye exposure may benefit from regular application of an anticholinergic ophthalmic ointment to prevent synechiae formation. A topical antibiotic/steroid ointment should be applied every 1-2 hours with rapid referral to an ophthalmologist. Ointment application to the lids prevents them from sticking together and can help prevent adhesions while allowing drainage of any underlying infection or pus. Blepharospasm can be treated with topical anesthetics to facilitate the eye exam, and systemic analgesics should be given for ongoing eye pain.

If patients have respiratory symptoms hours after the exposure, they should be treated as chemical pneumonitis; albuterol should aggressively be utilized, and invasive airway management should be considered early in the treatment plan if the patient is not responding to albuterol. Systemic steroids have been recommended if albuterol is not effective, but further immune suppression may not be advisable. Inhaled sodium bicarbonate has been suggested as a possible treatment as well, but there is not robust evidence to support its use. Other antioxidants and scavengers such as sodium thiosulfate have shown some benefit in animal studies, but there is no human data to support their use. These therapies should only be considered in patients’ refractory to supportive care when the benefit of unproven therapy outweighs potential risks.

Bone marrow suppression usually peaks around 9-10 days. Granulocyte colony stimulating factor analogues may be administered. Severe bone marrow suppression may be an indication for bone marrow transplant.

The antidote for Lewisite is British Anti-Lewisite (BAL), also known as Dimercaprol. BAL should only be used in a hospital setting and is given as an IM injection. BAL is a chelating agent, but due to the possibility of severe acute renal failure and other side effects, BAL is only recommended for patients who have severe respiratory symptoms or Lewisite shock.