Chemical warfare agents (CWAs) comprise a diverse group of extremely hazardous materials.[1] As potential weapons of mass destruction, CWAs are capable of causing a catastrophic medical disaster that could overwhelm any healthcare system.
Since civilian victims exposed to CWAs are likely to flee to the nearest hospital, emergency physicians play a key role in preparing emergency departments for the treatment of persons exposed to CWAs. Emergency physicians should be familiar with the pathophysiology and various clinical presentations produced by CWAs as well as the principles and practices of appropriate medical management.
This article reviews the physical properties and general clinical effects of CWAs. It also describes the medical management of victims of CWAs, including the use of personal protective equipment (PPE), victim decontamination, provision of supportive care, and provision of specific antidotal therapy. To illustrate these principles with specific agents, the properties, clinical effects, and medical management of nerve agents and vesicant agents are reviewed briefly.
The Chemical Hazards Emergency Medical Management (CHEMM) portal sponsored by the National Library of Medicine provides comprehensive information on chemical incident management, including specific information for first responders, hospital providers, and incident preparedness, as well as the general public. For patient education information, also see the First Aid and Injuries Center, as well as Chemical Warfare and Personal Protective Equipment.
Injury from CWAs may result from various sources including industrial accident,[2] inadvertent contact with chemical-laden shells from an unknown military dump site, military stockpiling, war, or terrorist attack.
Accidents involving toxic industiral chemicals continue to be a significant potential source of exposure to those agents that were also used as chemical warfare agents. Chemicals such as phosgene, cyanide, anhydrous ammonia, and chlorine are important precursors for manufacturing many products including plastics and agricultural products, and are widely and frequently transported. The accidental release of a methylisocyanate cloud (composed of phosgene and isocyanate) was implicated in the Bhopal disaster in 1984. These accidents continue today, with nearly 9000 occurring in the United States in 2001 alone.
In the modern warfare era, CWAs were first used in World War I in 1915 when the German military released 168 tons of chlorine gas at Ypres, Belgium, killing an estimated 5000 Allied troops. Two years later, the same battlefields saw the first deployment of sulfur mustard. Sulfur mustard was the major cause of chemical casualties in World War I. CWAs have been used in at least 12 conflicts since, including the first Persian Gulf War (Iraq-Iran War). The Iraqi military also used chemical weapons against the Iraqi Kurds during the second Persian Gulf War.[3, 4]
Civilians have also been exposed inadvertently to chemical weapons many years after weapons deployment during war. Approximately 50,000 tons of mustard shells were disposed of in the Baltic Sea following World War I. Since then, numerous fishermen have been burned accidentally while hauling leaking shells aboard boats.[5] Leaking mustard shells also have injured collectors of military memorabilia and children playing in old battlefields.
Although the Chemical Weapons Convention and a number of international treaties have banned the development, production, and stockpiling of those CWAs with only a warfare use, these agents reportedly still are being produced or stockpiled in several countries.
Within the last several decades, terrorists have deployed chemical weapons against civilian populations. The release of sarin in Matsumoto, Japan, in June 1994 by the extremist Aum Shinrikyo cult left 7 dead and 280 injured.[6, 7] The following year, in March 1995, the Aum Shinrikyo cult released sarin vapor in the Tokyo subway system during morning rush hour, leaving 12 dead and sending more than 5000 casualties to local hospitals.[8, 9, 10]
A derivative of fentanyl was also used against terrorists holding hostages in a Moscow theater in 2002. Because of a lack of antidote available by the responders, more than 120 casualties from asphyxiation occurred among the hostages.[7]
CWAs lend themselves to terrorist use because of several characteristics, as follows:
CWAs comprise a diverse group of hazardous substances. Major categories of CWAs include the following:
CWAs generally are stored and transported as liquids and deployed as either liquid aerosols or vapors. Victims usually are exposed to agents via one or more of three routes: skin (liquid and high vapor concentrations), eyes (liquid or vapor), and respiratory tract (vapor inhalation).
CWAs are characterized by two inversely related physical properties: volatility (ie, tendency of liquids to vaporize, which directly increases with temperature) and persistencet (ie, tendency of liquids to remain in a liquid state).
In general, volatile agents or aerosolized liquids pose the dual risk of dermal and inhalation exposure, while persistent liquids are more likely to cause exposure through direct contact with a contaminated surface and absorbed across the skin, or must be effectively aerosolized. The effects of vapors and aerosols are largely influenced by ambient wind conditions; even a slight breeze can blow nerve agent vapor away from its intended target. Effects of vapor or aerosols are enhanced markedly when deployed within an enclosed space.
Depending on the agent, exposure route, time, and amount (concentration) of exposure, CWA effects may be immediate or delayed.[13] Large inhalation exposures to nerve agents or mustards are likely to be lethal immediately. Small dermal exposures to nerve agents and mustards are particularly insidious and generally require expectant observation for variable periods because of possible delayed effects. Environmental factors can also impact exposure. Specific clinical effects of CWAs are as varied as the agents.
To manage CWA exposures appropriately, emergency care personnel must protect themselves by performing the following:
The primary responsibility of those who treat victims of CWAs is to protect themselves by wearing adequate PPE. First responders are at serious risk from the chemically contaminated environment (hot zone), either from direct contact with persistent liquid or from inhaling vapor. First responders and emergency care providers also are at risk of cross contamination from handling skin and clothing of victims contaminated with liquid CWAs (secondary skin and inhalation exposure). Conversely, providing care to those exposed only to vapor CWAs poses little risk to emergency care providers outside the hot zone. Regardless, until the substance is identified and deemed nontoxic, responders should wear the appropriate level of PPE.
Standard protective garments are inadequate for most CWAs. Double layers of latex gloves do not provide adequate protection against liquid nerve and blister agents, and surgical masks and face masks are inadequate against CWA vapors or aerosols.
US regulatory agencies mandate the use of appropriate levels of PPE. The Occupational Safety and Health Administration (OSHA) lists three levels for Hazardous Waste Operations (HAZWOPER), as follows[14] :
Decontamination is thel process of physically removing or neutralizing residual chemicals from persons, equipment, or the environment. Residual hazardous chemicals on those who have been exposed directly are a source of ongoing exposure to those persons and pose a risk of cross contamination and secondary exposure to first responders and first receivers. Immediate decontamination is a major treatment priority for those with CWA exposure. National planning guidance for communities has recently been promulgated.[16]
Initial decontamination involves removal from the contaminated environment, removal of all contaminated clothes and jewelry, and copious irrigation with water. Avoid hot water and vigorous scrubbing, as they may increase chemical absorption. Current recommendations no longer favor the use of dilute bleach solutions for patient decontamination.
Vapor exposure alone does not require decontamination. Fully decontaminate patients with unclear exposure histories. As well, if a nerve agent is suspected, decontamination should be performed as the patient may off-gas significant levels of the agent with the potential of ongoing exposure and to the patient and caretakers.
Ideally, perform decontamination as close as possible to the site of exposure to minimize duration of exposure and prevent further spread. Hospitals receiving contaminated persons should establish an area outside the emergency department in which to perform decontamination before people and equipment are allowed in. Portable decontamination equipment with showers and run-off water collection systems are commercially available. All hospitals should have the capacity to safely decontaminate at least one person.
The level of decontamination capability is generally determined through a standard hazard and vulnerability assessment for the hospital coordinated within the community through the local emergency preparedness committee.
Supportive therapy for victims of CWAs generally follows the universally accepted algorithm of first ensuring the adequacy of airway, breathing, and circulation, with one important exception: severe nerve agent poisoning may require immediate administration of parenteral atropine. Many CWAs can be treated with supportive care only. Specific, well-established antidotes are available only for nerve agent and cyanide exposures. Since no laboratory tests are available to rapidly confirm exposure to CWAs, treatment is based on clinical criteria.
The nerve agents, including tabun (GA), sarin (GB), soman (GD), cyclosarin (GF), and VX, have chemical structures similar to the common organophosphate pesticide malathion. Like organophosphate insecticides, these agents phosphorylate and inactivate acetylcholinesterase (AChE). Acetylcholine accumulates at nerve terminals, initially stimulating and then paralyzing cholinergic neurotransmission throughout the body.[17]
Inhibition of AChE may not account for all of the toxic effects of nerve agents. These agents also are known to bind directly to nicotinic receptors and cardiac muscarinic receptors. They also antagonize gamma-aminobutyric acid (GABA) neurotransmission and stimulate glutamate N -methyl-d-aspartate (NMDA) receptors. These latter actions may partly mediate nerve agent–induced seizures and CNS neuropathology.
Under temperate conditions, all nerve agents are volatile liquids. The most volatile agent, sarin, evaporates at approximately the same rate as water. The least volatile agent, VX, has the consistency of motor oil. This persistence and higher lipophilicity make VX 100-150 times more toxic than sarin when victims sustain dermal exposure. A 10-mg dose applied to the skin is lethal to 50% of unprotected individuals.
All nerve agents rapidly penetrate skin and clothing. Nerve agent vapors are heavier than air and tend to sink into low places (eg, trenches, basements).
Nerve agents produce muscarinic, nicotinic, and direct CNS toxicity with a wide variety of effects on the respiratory tract, cardiovascular system, CNS, gastrointestinal (GI) tract, muscles, and eyes. Onset and severity of clinical effects vary widely, since numerous variables determine predominant effects. Agent identity, dose (determined by concentration and duration of exposure), and type of exposure primarily determine nerve agent toxicity. Toxic effects result from dermal exposure to liquid and ocular and inhalation exposure to vapor.
Liquid exposure
Liquid agents easily penetrate skin and clothing. Onset of symptoms occurs from less than 30 minutes to longer than 18 hours following dermal exposure depending on agent, dose, concentration, depth of skin.
Minimal liquid exposure (eg, a small droplet on the skin) may cause local sweating and muscle fasciculation, followed by nausea, vomiting, diarrhea, and generalized weakness. Even with decontamination, signs and symptoms may persist for hours. Decontamination cannot remove agent already penetrating through the skin and can actually increase the absorption gradient for agent in the skin.
In contrast, persons with severe liquid exposures may be briefly asymptomatic (1-30 min) but rapidly may suffer abrupt loss of consciousness, convulsions, generalized muscular fasciculation, flaccid paralysis, copious secretions (nose, mouth, lungs), bronchoconstriction, apnea, and death.
Vapor exposure
Vapor and aerosol inhalation produces clinical toxicity within seconds to several minutes. Effects may be local or systemic. Exposure to even a small amount of vapor usually results in at least one of the following categories of complaints: (1) ocular (miosis, blurred vision, eye pain, conjunctival injection), (2) nasal (rhinorrhea), or (3) pulmonary (bronchoconstriction, bronchorrhea, dyspnea).
Exposure to a vapor concentration of 3.0 mg/m3 for 1 minute causes miosis and rhinorrhea. Inhalation of a high concentration of vapor results in loss of consciousness after only one breath, convulsions, respiratory arrest, and death. For example, breathing 10 mg /m3 of sarin vapor for only 10 minutes (100 mg/m3 for 1 min) causes death in approximately one half of exposed individuals. Severe vapor exposures also are characterized by generalized fasciculations, hypersecretions (mouth, lungs), and intense bronchoconstriction with respiratory compromise.
Respiratory tract
Nerve agents act on the upper respiratory tract to produce profuse watery nasal discharge, hypersalivation, and weakness of the tongue and pharynx muscles. Laryngeal muscles are paralyzed, resulting in stridor. In the lower respiratory tract, nerve agents produce copious bronchial secretions and intense bronchoconstriction. If untreated, the combination of hypersecretion, bronchoconstriction, respiratory muscle paralysis, and CNS depression rapidly progresses to respiratory failure and death. Nerve agents depress the central respiratory drive directly. Thus, early death following large vapor exposure likely results from primary respiratory arrest, not from neuromuscular blockade, bronchorrhea, or bronchoconstriction.
Cardiovascular system
The cardiovascular effects of nerve agents vary and depend on the balance between their nicotinic receptor–potentiating effects at autonomic ganglia and their muscarinic receptor–potentiating effects at parasympathetic postganglionic fibers that innervate the heart.
Sinus tachydysrhythmias with or without hypertension (sympathetic tone predomination) or bradydysrhythmias with or without variable atrioventricular blockade and hypotension (parasympathetic tone predomination) may occur.
Superimposed hypoxia may produce tachycardia or precipitate ventricular tachydysrhythmias.
Nerve agent–induced prolonged QT and torsades de pointes have been described in animals.
In victims of the Tokyo sarin gas attack, sinus tachycardia and hypertension were common cardiovascular abnormalities, while sinus bradycardia was uncommon.
Central nervous system
Nerve agents produce a variety of neurologic signs and symptoms by acting on cholinergic receptors throughout the CNS. The most important clinical signs of neurotoxicity are a rapidly decreasing level of consciousness (sometimes within seconds of exposure) and generalized seizures. Symptoms such as headache, vertigo, paresthesias, anxiety, insomnia, depression, and emotional lability also have been reported.
Musculoskeletal system
Nerve agents initially stimulate and then paralyze neurotransmission at the neuromuscular junction. With minimal exposure, exposed persons may complain of vague weakness or difficulty walking. More significant exposures resemble the clinical effects that result from succinylcholine, with initial fasciculations followed by flaccid paralysis and apnea.
Ocular
Nerve agent liquid or vapor readily penetrates the conjunctiva and exerts direct muscarinic parasympathetic effects. This results in constriction of the iris (miosis, blurred and dim vision, headache), constriction of the ciliary muscle (pain, nausea, vomiting), and stimulation of the lacrimal glands (tearing, redness). Although miosis is the most consistent clinical finding after vapor exposure to nerve agents (occurred in 99% of persons exposed in Tokyo sarin attack), it may be absent or delayed in dermal exposure. Duration of miosis varies according to the extent of ocular exposure (up to 45 d).
Routine toxicology testing does not identify nerve agents in serum or urine. Measurements of red blood cell (RBC) or plasma cholinesterase activity have been used as an index of the severity of nerve agent toxicity, but this approach is not always reliable. The reference range of RBC cholinesterase activity may vary widely, and mild exposures may be difficult to interpret without baseline measurement. In addition, RBC cholinesterase activity may not correlate with the severity of signs and symptoms following vapor exposure.
In the Tokyo subway sarin attack, 27% of patients with clinical manifestations of moderate poisoning had plasma cholinesterase activity in the normal range. Moreover, different organophosphates variably inhibit RBC and plasma cholinesterase. For example, in mild-to-moderate exposures to sarin or VX, RBC cholinesterase activity is decreased to a much greater extent than plasma cholinesterase activity.
Since plasma cholinesterase is produced by the liver, its activity also may be depressed in certain conditions (eg, liver disease, pregnancy, infections) or with certain drugs (eg, oral contraceptives). Conversely, a 20-25% reduction in RBC cholinesterase activity tends to correlate with severe clinical toxicity and, despite the exception noted above, activity of both enzymes approaches zero in most severely poisoned victims. Nevertheless, treatment decisions should be clinically based. Never withhold treatment from a symptomatic patient while awaiting laboratory confirmation. Conversely, decreased cholinesterase activity in the absence of clinical signs of toxicity is not an indication for treatment.
First responders are at serious risk of exposure within the contaminated environment (hot zone), either from direct contact with persistent liquid or from inhaling residual vapors. First responders and subsequent emergency care providers outside the hot zone and first receivers based at the hospital are at risk from handling persons contaminated with liquid nerve agent (through both dermal and inhalation exposure).
Conversely, victims exposed to nerve agent vapor pose little risk to emergency care providers outside the hot zone; residual agent is not present and off-gassing may occur but rarely in clinically significant amounts. Disrobing of the victims provides significant reduction in agent and risk to first receivers being exposed. In the Tokyo sarin attack, approximately 90% of exposed persons reported to medical facilities by private or public transportation without notable contamination of others. Additionally, secondary injury to hospital staff was minimal and did not necessitate specific treatment.
Unless a clear history of vapor exposure only is obtained, emergency medical personnel should assume that liquid contamination is present and wear the appropriate level of PPE. For most nerve agent exposures, first responders require level A PPE inside the hot zone, and first receivers at hospitals involved in decontamination should wear level B or, more likely, level C PPE.[15, 16]
Significant updates have been made on patient decontamination in mass chemical exposure incidents.[16] Generally, the approach is to decontaminate withtepid water or soap and water and thorough water rinsing. In survivors, the amount of residual liquid contaminant is likely to be small, because victims with larger exposures probably will die before they reach the hospital. Other than removing clothing and jewelry, decontamination is usually unnecessary for victims of vapor nerve agent exposure; however, agent dispersed as an aerosol may present as vapor at the incident site but deposit agent on the skin that represents an exposure hazard to first receivers.
Saving lives always depends on ensuring adequate airway, ventilation, and circulation. The larger the exposure, the more likely victims require early intubation and ventilation. Conversely, adequate ventilation may be impossible due to the intense muscarinic effects of nerve gas exposure (copious airway secretions, bronchoconstriction). In this situation, administration of atropine is the critical step. The use of succinylcholine to assist intubation is not recommended, since nerve agents prolong the drug's paralytic effects.
Treat seizures with adequate oxygenation and aggressive use of benzodiazepines titrated to effect. Termination of seizure activity may reflect onset of flaccid paralysis from the nerve agent rather than adequacy of antiseizure therapy. A bedside electroencephalograph (EEG) may be required to assess ongoing seizure activity.
Animal data suggest that routine administration of diazepam reduces incidence of seizures and decreases severity of pathologic brain injury following nerve agent exposure. Midazolam may have faster onset of action and better CNS penetration and is curently under evaluation for FDA approval for the treatment of seizures caused by nerve agents..
Treatment of victims with nerve gas toxicity is broadly similar to the treatment of those poisoned by organophosphate insecticides.
Atropine sulfate
Symptomatic patients require immediate treatment. Atropine blocks muscarinic effects of nerve agents (eg, bronchorrhea, bronchoconstriction), improving ventilation by drying secretions and decreasing airway resistance. Atropine also blocks other muscarinic effects, such as nausea, vomiting, abdominal cramping, bradycardia, and diaphoresis. Atropine does not have nicotinic effects and thus does not reverse toxicity at autonomic ganglia and neuromuscular junctions. Atropine does not prevent or reverse paralysis.
Atropine therapy is guided by clinical signs and symptoms. Titrate dosing to the desired clinical effect. The goals of atropine therapy are to dry secretions and eliminate bronchoconstriction.
Administer more atropine if assisted ventilation remains difficult or secretions persist. Heart rate and pupil size are poor clinical indicators of adequate atropinization. Presence of tachycardia should not dissuade the clinician from initiating or continuing atropine therapy. Miosis may be absent or delayed in dermal exposures and is not reversed by systemic atropine.
Up to 20 mg of atropine may be required the first day, unlike with organophosphate insecticide poisoning, where as much as 3000 mg of atropine may be required over 1 day. In the Tokyo sarin attack, only 19% of poisoned patients required more than 2 mg of atropine. Severely poisoned patients required 1.5-15 mg of atropine.
Oxime therapy
Oximes are nucleophilic substances that bind to the phosphate moiety of the nerve agent more avidly than AChE to reactivate the nerve agent–inhibited enzyme. Reactivation is impossible once dealkylation or "aging" of phosphorylated AChE occurs. Once aging occurs, new AChE must be synthesized. The rate of aging varies among nerve agents. Aging occurs within 2 minutes after soman exposure, 5-8 hours after sarin exposure, and more than 40 hours after tabun and VX exposure.
Pralidoxime chloride (2-PAM) is the only conventional oxime available for clinical use in the US. Administer pralidoxime to symptomatic patients as early as possible, ideally concurrent with adequate doses of atropine. Pralidoxime has its greatest effect at the neuromuscular junction.
Slowly administer pralidoxime IV to minimize adverse effects such as hypertension, headache, blurred vision, epigastric pain, nausea, and vomiting. When IV access cannot be established, 2-PAM also may be given IM (1 mg with 3 mL sterile saline).
With adequate decontamination and appropriate initial therapy, serious signs and symptoms of nerve agent toxicity rarely last more than a couple of hours. In the unusual event that toxicity persists or worsens clinically, administer repeat doses of 2-PAM at hourly intervals. In the Tokyo sarin attack, severely poisoned patients required 1-36 g. Since 2-PAM is excreted in the urine, lower repeat doses for patients with renal failure and maintain adequate hydration. If hypertension increases during pralidoxime administration, IV phentolamine may help (adults: 5 mg IV; children: 1 mg IV).
Mark I kit
The Mark I kit (atropine/pralidoxime) was designed for military self-administration in the field. It consists of two spring-loaded IM autoinjectors containing 2 mg of atropine and 600 mg of pralidoxime, respectively. These antidote kits are not yet available for civilian use.
Duodote
Duodote is a single autoinjector that contains both 600 mg of pralidoxime and 2 mg of atropine.
Hemodialysis
Japanese physicians reported successful use of hemodialysis and hemoperfusion in one severely intoxicated victim of the Tokyo Subway sarin attack who remained unresponsive to pharmacotherapy.
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 be discharged. Unlike with organophosphate insecticides, nerve agents have not generally been associated with delayed neuropathy, although a study of Iranian veterns exposed to tabun during the Iran/ Iraq war suggests a possible exception.[3]
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.
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.
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.[18, 19] 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.[20]
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.
Diagnosis of mustard exposure is clinical. No laboratory tests identify or characterize acute exposure.
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 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. 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.
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. Fluid in blisters does not contain mustard agent because it becomes fixed rapidly to tissue; however, this is not the case for Lewisite, were agent may accumulate in low doses.
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.
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.
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 marrow suppression. Sulfur mustard is a known carcinogen, yet a single exposure causes only minimal risk.