With the attacks on the World Trade Center and Pentagon on September 11, 2001, followed soon after by the postal anthrax attacks by unknown assailants, the "unthinkable" has become reality. The eyes of the American public have been opened to the vulnerability of its society to terrorism in all of its forms. Much of the focus has been on biologic and chemical agents (eg, nerve agents), especially with revelations that terrorist groups may possess some technology required for weapons of mass destruction (more properly, mass-casualty weapons). However, an equally potent, and possibly more likely, scenario is the terrorist use of industrial chemicals as weapons. Because of the potential threat posed by toxic industrial chemicals, it is important for pediatricians to understand the properties of these chemical weapons of opportunity. Medical management of injuries by industrial chemicals requires familiarity with the characteristics of the agents and with clinical effects of exposures, as well as the unique aspects of care of pediatric casualties. Although there are numerous agents that may be weaponized, the following discussion focuses on chlorine and phosgene - industrial chemicals that historically have been used as weapons.
In 1999, Federal Bureau of Investigation agents arrested members of a domestic anti-government terrorism group that were planning to attack a large propane storage facility in Elk Grove, California. An attack on this facility, located near a large residential area, would have released a toxic cloud of gas causing death and injuries in hundreds, if not thousands, of innocent people, including children.1 The group's "technology" consisted of detonating cord, blasting caps, grenade hulls, and various chemicals such as ammonium nitrate.
Much of the public attention on chemical terrorism has been focused on nerve agents such as tabun, sarin, and VX. However, toxic industrial chemicals pose a less apparent but equally potential threat to be used as terrorist weapons. The Chemical Weapons Convention, a disarmament and nonproliferation treaty with 145 signatory countries, identified 33 chemical and chemical precursors that can be used as weapons. While some of the chemicals are well-known weapons - sarin, VX, sulfur mustard - others are more familiar as common industrial chemicals, eg, chlorine and phosgene.2 In the United States millions of tons of chlorine and phosgene are manufactured yearly for the production of dyes, textiles, medicines, insecticides, solvents, paints, and plastics.
What is the potential terrorist threat posed by industrial chemicals, compared to other better-known weapons of mass destruction? In a January 2002 report to Congress, the Central Intelligence Agency reported that terrorist groups have a "lesser interest in biological materials," which may be used in "small-scale poisoning or assassinations;" however, these groups "are most interested in chemicals such as cyanide salts to contaminate food and water supplies... Terrorist groups also have expressed interest in many other toxic industrial chemicals - most of which are relatively easy to acquire and handle - and traditional chemical agents, including chlorine and phosgene."3
Although of clear interest to terrorist groups, nerve agents require a greater degree of technical sophistication to manufacture and deliver these chemicals as weapons. In Japan, the cult Aum Shinrikyo, despite $1 billion in assets and the technical expertise of universitytrained scientists, launched two nerve agent attacks that resulted in relatively few (less man 20) deaths.
This threat is a significant concern of the United States government A Washington Post article in December 2001 summarized the findings of several Environmental Protection Agency documents outlining dozens of frightening scenarios: rupture of a 90-ton rail car with chlorine in Los Angeles and Orange County, California, would potentially poison four million people; a Philadelphia refinery with 400 000 pounds of hydrogen fluoride could asphyxiate nearly four million people if released; a New Jersey chemical plant has enough chlorine that, if released, could form a poisonous cloud endangering 12 million people.4 Because of these and other scenarios, government and industry officials have worked to replace dangerous chemicals with safer substitutes when feasible and have focused on increasing security where substitutions are not possible.
Although not stockpiled in the United States for military purposes chlorine and phosgene are common components in industrial manufacturing. Chlorine is a common industrial chemical used in water purification, bleaches, and in manufacturing organic compounds. Phosgene is commonly used in manufacturing dyes, pesticides, and plastics. Primarily liquids, they are easily vaporized, allowing for widespread gaseous dispersion.
Chlorine was the first chemical agent used on a large scale in modem warfare. In April 1915, near the town of Langemarck in the Ypres salient of Belgium, the German Army released 168 tons of chlorine across British lines. Surprised by its success, the German Army was unprepared to exploit the break in the British defenses, and the British quickly restored the lines. This attack, however, marked the beginning of the extensive use of chemical weapons on the battlefield. World War I saw widespread use of chlorine, phosgene, diphosgene, hydrogen cyanide, cyanogen chloride, and sulfur mustard as offensive weapons.5
As chemical weapons, chlorine and phosgene are commonly known as pulmonary, inhalational, or choking agents. These terms are ambiguous, and it is better to conceptualize these compounds along a spectrum that includes Type I and Type II agents. Type I agents act primarily on the proximal (tracheobronchial) components of the respiratory tract and Type II agents act primarily on the peripheral (gas-exchange) regions, ie, respiratory bronchioles, alveolar ducts, and alveoli. Type I agents are typically water-soluble, chemically reactive substances that attack the respiratory epithelium of the bronchi and larger bronchioles, leading pathologically to necrosis and denudation with or without the formation of pseudomembranes. Clinically mucosal irritation and prominent components of noise (coughing, sneezing, hoarseness, inspiratory stridor, and wheezing) occur. Type II agents cause noncardiogenic pulmonary edema that initially manifests clinically as dyspnea without accompanying signs or radiological or laboratory anomalies.
Few agents are pure Type I or Type II, and high doses of either kind of agent can cause effects in both proximal and peripheral respiratory compartments. For example, chlorine, which is intermediate in both aqueous solubility and in chemical reactivity, typically produces a mixture of proximal and peripheral effects. Phosgene, however, has few Type I effects except at moderately high doses. Sulfur mustard is poorly soluble in aqueous media, but once dissolved, it cyclizes to form such a powerfully reactive cyclic ethylene sulfonium oxide that it acts in the airways primarily as a Type I agent at low to moderate doses. If used as weapons of mass destruction, agents such as hydrogen cyanide and hydrogen sulfide would most likely be released as vapors or gases and in that regard would be inhalational agents. However, in contradistinction to Type I and Type II agents, whose major pathological and clinical effects are local (topical) on respiratory epithelium or alveolar septa, cyanides are widely distributed hematogenously to all tissues and organs of the body and therefore merit a separate classification as Type HJ (systemically distributed) agents.
Finally, some agents (sulfur mustard is a good example) exhibit both local (in this case, initially Type II) and systemic (Type III) effects. In the case of sulfur mustard, the systemic effects (which may include bone-marrow depression and resultant pancytopenia6) become clinically significant only after a delay.
Chlorine is a greenish-yellow, heavier-than-air gas that settles close to ground and low-lying areas when released. This may have significant consequences for smaller children and infants in strollers who may be exposed. Such children would be exposed to higher concentrations of chlorine vapor and would thus receive higher inhaled doses of the agent. Chlorine has a strong, pungent odor that most people associate with swimming pools. Because the odor threshold at 0.08 parts per million is less than the toxicity threshold, the aroma may provide adequate warning for individuals who are exposed.
Phosgene, like chlorine, is also heavier than air, thus posing an increased risk for children who are exposed. Although it is colorless, associated condensation of atmospheric water produces a dense white cloud that settles low to the ground. It has the characteristic odor of newly mown hay. However, unlike chlorine, the odor threshold for phosgene at 1.5 parts per million is higher than the toxicity threshold and detection of the odor is inadequate to protect against toxic exposure.
The initial complaints in a chlorine exposure situation may be either intense irritation or the sensation of suffocation, or both; the suffocating feeling is what led to its characterization as a choking agent. Low-level exposures to chlorine result in mucosal irritation of the upper-airway nasal membranes and ocular membranes. Higher doses induce additional respiratory complaints that are classically Type I effects progressing from choking and coughing, to hoarseness, aphonia, and stridor. Dyspnea in chlorine exposures indicates peripheralcompartment damage (Type II insult) and incipient pulmonary edema.
The significant morbidity from pulmonary agents results from development of pulmonary edema. With chlorine, pulmonary edema may appear within 2 to 4 hours, sooner with more significant exposures. Radiologic signs lag behind clinical symptoms: It takes a five-fold to six-fold increase in pulmonary interstitial fluid to produce Kerley B lines on a chest radiograph. The pulmonary edema may be exceptionally profuse; a study from the 1940s noted that pulmonary sequestration of plasma-derived fluid with volumes up to 1 L/h might result.7 For children, this problem may be particularly profound. With smaller fluid reserve, the exposed child is at increased risk for rapid dehydration or frank shock with the development of pulmonary edema. Additionally, because of the pediatric casualty's normally faster respiratory rate, there is exposure to a relatively higher toxic dose.
Phosgene is primarily a pulmonary edematogenic, and, because in low to moderate doses it does not cause the mucosal irritation associated with Type I agents, the significance of the exposure may be underestimated. Exposure to progressively higher doses produces mild cough, sneezing, and other proximal-compartment effects. Dyspnea is seldom present initially except in massive doses; instead, there is a clinically asymptomatic or latent period usually of several hours and inversely correlated with dose. Dyspnea and associated clinical deterioration have been triggered by slight to moderate exertion in several instances.6,8
Unlike some potential biochemical agents for which there is only very limited experience in the Western world, the treatment of toxic inhalational agent exposures in children has been well documented as the result of many accidental exposures.6,9,10
In pulmonary agent exposures, decontamination consists primarily of removal of the victim from the source and exposure to fresh air. For first responders such as paramedics and fire-rescue workers, personal protective equipment with selfcontained breathing apparatus is required; however, because the gases are volatile, cross-contamination is unlikely. Chlorine exposures may require copious water irrigation of the skin, eyes, and mucosal membranes to prevent continued irritation and injury. Currently, management is primarily supportive; there are no antidotes or specific postexposure treatments for inhalational agents. Careful attention to the respiratory system is required, and this must include observation and monitoring for both proximal (Type I) and peripheral (Type LT) acute effects, including the development of pulmonary edema. Most deaths are due to respiratory failure and usually occur within the first 24 hours. Because of the delayed onset of pulmonary edema, prolonged observation for victims of phosgene and chlorine attacks is warranted.
Treatment of proximal (Type I) damage involves administration of warm, moist air, supplemental oxygen, and treatment of bronchospasm either produced de novo by the toxicant in normal airways or the result of toxicant-induced exacerbation of airway hyperresponsiveness in individuals with underlying pathology such as asthma or reactive airways. Aggressive bronchodilator therapy with β-agonists is appropriate. Of less clear value is the use of corticosteroids, which may be efficacious in victims with severe bronchospasm or a history of asthma. Nebulized lidocaine (4% topical solution) has been recommended to provide analgesia and to reduce coughing.
The possibility of laryngospasm should always be anticipated and should lead to a careful assessment of the necessity and timing of intubation. Associated proximal respiratory damage from inhaled particles of smoke in situations involving fire must also be considered. Pseudomembrane formation may lead to airway obstruction and may require bronchoscopic identification and removal of pseudomembranous debris.
Necrotic debris from proximal damage provides an excellent culture medium for secondary bacterial colonization and infection. Although prophylactic antibiotics are not of value, bacterial superinfections are commonly seen 3 to 5 days after exposure. Early aggressive antibiotic therapy directed against culture-identified organisms is imperative.
The mainstays of the treatment of peripheral (Type II) damage from pulmonary agents remain adequate oxygenation, establishment of effective intra-alveolar pressure grathents using positive endexpiratory pressure (eg, in conscious patients, with continuous positive airway pressure), and careful attention to fluid balance. In cases of florid pulmonary edema, a central venous line in the pediatric intensive care unit may be necessary to monitor hemodynamics. The length of the latent period in a dyspneic patient can provide clinically valuable information about the intensity of exposure; patients who develop difficulty breathing within the first 4 hours after exposure may face a grave prognosis, and even patients with mild dyspnea (apparent early) may be candidates for urgent or priority evacuation because of the timing of dyspnea. All patients at risk for pulmonary edema induced by pulmonary agents should also be maintained at strict bed rest to avoid exertion-associated cardiopulmonary decompensation.
The damage caused by terrorist weapons is not limited to damage of property and the loss of human life but also encompasses the fear and emotional scars instilled by the attack itself. Although the deaths of thousands in the World Trade Center collapse can never be measured in terms of dollars, the impact of the attacks ranged far beyond Manhattan. The federal air transport system was grounded, the nation's economy took a slide from which it has not yet recovered, and the everyday lives of many citizens have been impacted by increased security measures taken by airports and public facilities. Terrorism seeks not only to kill but also to frighten and disrupt. Any attack, regardless of its magnitude, has the potential to overwhelm a community's medical resources.
The first step in mitigating this chemical agent threat is improving the security at industrial plants, water treatment plants, railheads, harbors, and other facilities where industrial chemicals are used, stored, and transported. Both government and industry are working together to identify and address shortcomings in security at these locations. However, given the improbability of a completely fail-safe system, emergency medical systems and health care organizations must be prepared for mass-casualty events as a result of industrial accidents, either accidental or volitional. History has taught us that children may compose a significant portion of the casualties in a civil disaster. In any domestic terrorist attack, pediatricians undoubtedly will be a critical factor in the medical emergency response.
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2. Organisation for the Prohibition of Chemical Weapons. Mission statement of the Oragnisation for the Prohibition of Chemical Weapons (OPCW). Available at: www.opcw.org/html/ glance/index.html. Accessed: February 28, 2003.
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