Chemical Agents of Mass Destruction

James Geiling

Lawrence C. Mohr Jr

If supposedly civilized nations confined their warfare to attacks on the enemy’s troops, the matter of defense against warfare chemicals would be purely a military problem, and therefore beyond the scope of this study. But such is far from the case. In these days of total warfare, the civilians, including women and children, are subject to attack at all times.

—Colonel Edgar Erskine Hume, Medical Corps, U.S. Army, 1943 [1]

Chemical agents of terror have moved to the forefront of concern for healthcare providers as weapons of mass destruction (WMD) have become readily available to both domestic and international terrorists. Critical care physicians must be familiar with these agents, their impact on patients, and the potential dangers these compounds can cause to healthcare workers.

Although terrorists have traditionally focused their efforts on the use of conventional explosives, chemical agents have emerged as attractive weapons of terrorism for a variety of reasons:

Raw materials for their production are readily available throughout the world.
Raw materials are inexpensive.
A chemical weapon of mass destruction can be produced with relatively small amounts of raw materials.
They may be odorless, colorless, and tasteless.
They are poorly detected.
They do not destroy infrastructure.
They possess a latency period between the time of exposure and the development of clinical symptoms.
Their use produces a mass media response [2].

Hospital-based physicians normally, at some time in their medical career, study the skills and procedures needed to treat mass casualties. The focus, however, has traditionally centered on large numbers of casualties presenting to the emergency department as a result of multisystem trauma, such as that sustained in an explosion, airplane crash, or natural disaster. The event of September 11, 2001, and subsequent terrorist threats have changed the nature of physician training and preparation requirements. The scope of preparation now requires knowledge of the mass care of victims following a WMD event. This chapter focuses on the recognition and management of patients exposed to common chemical agents of mass destruction.

History

Chemical agents of mass destruction are gaseous, liquid, or solid substances that are employed against a population because of their direct toxic effects. Virtually any toxic substance can be used as an agent of mass destruction. However, those that have been successfully weaponized are characterized by ease of production, ease of handling during weapon assembly, dispersion properties, and ability to cause injury and death in relatively low concentrations [3].

Although the first reported use of chemical agents dates back to 1000 BC, when Chinese forces used arsenical smokes, the use of chemical agents in warfare began in earnest during World War I when German forces seeking a breakout from the stalemate of trench warfare released 150 tons of chlorine gas from 6,000 cylinders on the afternoon of April 15, 1915, near Ypres, Belgium. The chlorine gas resulted in 800 deaths and caused the retreat of 15,000 Allied troops, largely because of the psychological terror produced by the gas attack.

The next major use of chemical weapons took place more than 2 years later, on July 12, 1917, again near Ypres. On that date, German forces attacked Allied troops with artillery shells containing sulfur mustard. This attack resulted in 20,000 casualties. Although many casualties had debilitating injuries, less than 5% of the troops died as a result of the chemical attack. Persistent and nonvolatile, sulfur mustard caused a host of new problems for Allied forces, including a latency period before the effects appeared and the need for men, and their horses, to wear protective overgarments [4].

The Geneva Convention of 1925 banned the use of chemical warfare agents because of the physical and psychological trauma they imposed on their victims.

Nerve agents appeared in the 1930s when the German industrial chemist, Dr. Gerhard Schrader, began research into the development of stronger insecticides, the first two of which were tabun and sarin. German forces stockpiled these for use in World War II, but never used them.

Chemical agents were used sporadically in the second half of the twentieth century. The United States used defoliants and riot-controlled agents in Vietnam. Iraq used mustard, tabun, and eventually sarin against Iran in the Iran–Iraq war of the 1980s. Later in the 1980s, reports implicated Iraq in the use of cyanide against the Kurdish population in northern Iraq [5].

The most recent publicized use of chemical agents took place in Japan when the Aum Shinrikyo religious cult released sarin gas on two occasions. The first took place on June 27, 1994, in Matsumoto and resulted in 600 persons exposed, 58 admitted to the hospital, and 7 deaths [6]. The more famous and larger event took place the following year, on March 20, 1995, when the cult released sarin gas in the Tokyo subway system during rush hour. The subway system attack resulted in the deaths of 11 commuters and the medical evaluation of approximately 5,000 individuals [7].

In 1997 the Chemical Weapons Convention (CWC) went into effect as an international treaty that bans the use, development, production, acquisition, transfer, stockpiling, and retention of chemical weapons by signatory nations. At the time of this writing, the CWC was ratified by 175 nations, including the United States. The CWC is administered by the Organization for the Prohibition of Chemical Weapons, which conducts regular inspections and monitors compliance with provisions of the treaty [8].

Detection and Decontamination

Initial steps in the management of chemical agent casualties include detection of the chemical agent used in the attack and the decontamination of casualties. Detailed discussions on detection and decontamination are beyond the scope of this chapter. However, hospital-based critical care physicians should understand basic concepts of these topics to better care for their patients and protect themselves and their facilities from potential harm.

The most important tool in detecting the use of these agents is accurate and timely intelligence from military or law enforcement agencies. Unfortunately, hospitals are not usually in the information-sharing and decision-making circles with these groups. As a result, initial awareness of a chemical agent attack typically occurs with the first patient presenting to the emergency department. Hospitals and physicians can improve their preparedness for the management of chemical agent casualties by actively participating in disaster-planning activities in their respective communities.

Various types of sensing devices can be used for the detection of chemical agents in the environment. At the present time, all commercially available detection equipment uses point source technology; that is, proximity to the substance is required. The handheld Chemical Agent Monitor uses ion mobility spectrometry to detect mustard and nerve agents. Chemical agent detection papers, such as the M8 and M9 papers (Anachemia, Lachine, Quebec, Canada), can be used to detect mustard and nerve agents. The M256 Detection Kit (Anachemia, Lachine, Quebec, Canada) can detect mustard, nerve agents, phosgene, and cyanide. Standoff capability, that is, detecting agents from as far away as 5 km, has been developed to detect contaminated areas without being exposed [9]. Newer chemical agent detection technologies will continue to evolve in response to the terrorism threat. These can only help ensure hospitals and providers have quicker, more accurate information to meet the needs of victims.

Ideally, the decontamination of chemical agent casualties should be accomplished by first responders or hazardous material personnel prior to evacuation or transport to a medical facility. Unfortunately, most disaster victims bypass emergency medical system transport and arrive unannounced at the closest hospital. As a result, hospitals must be prepared to decontaminate chemical agent casualties prior to admission. Facilities and protocols to decontaminate such casualties should be developed by all hospitals. Such processes are needed to protect the victims from further exposure and to prevent the spread of chemical agents within the hospital and among healthcare providers. Critical care physicians, nurses, and support personnel may be called on to help develop decontamination protocols and assist in the decontamination process. It is imperative that all individuals designated to serve on decontamination teams be thoroughly trained in the procedures, precautions, and protective clothing required in the decontamination process. Attempting to provide help in a contaminated environment without prior training puts the healthcare provider at risk of being exposed to a chemical agent and could impede the delivery of effective medical care for the victims of a chemical attack.

The sarin gas release in Tokyo provides a clear example of the need for preparation and training prior to a chemical attack. Of the 1,364 emergency personnel who responded to the attack, 135 (9.9%) became symptomatic and required medical support themselves. None of the first responders wore protective clothing or face masks and off-gassing of the chemical agent from clothing of victims played a significant role in their complaints. These effects were evident among hospital staff as well first responders. It was reported that 23% of the staff at the hospital that received the patients also experienced symptoms [10].

The Occupational Safety and Health Administration (OSHA) mandates that all healthcare providers be trained to perform their duties without jeopardizing the health and safety of themselves or coworkers. It provides guidance for the use of personal protective equipment and requires that written plans be developed for hospitals to train teams in the use of personal protective equipment to receive contaminated victims [11]. Most medical facilities prepare their decontamination teams to operate in OSHA personal protective equipment Level C; that is, full-face mask with an air-purifying canister respirator and chemical-resistant clothing.

In most situations, effective chemical decontamination can be performed by carefully removing the victim’s clothing and thoroughly washing the victim with soap and water. It has been reported that removing contaminated clothing alone can eliminate 85% to 90% of chemical contaminants [12]. Recently developed for the military and soon to be used by first responders is Reactive Skin Decontamination Lotion (RSDL) (O’Dell Engineering Ltd/E-Z-EM Canada Inc., Canada). It is not used for prophylactic protection or total body decontamination, but, if applied early following exposure, is effective in neutralizing chemical warfare agents and T2 mycotoxins [13]. However, in exposures associated with trauma, RSDL may interfere with normal wound healing [14]. EasyDECON (Envirofoam Technologies, Huntsville, Alabama) can be used to decontaminate exposed environmental surfaces. Normally employed as a foam, it effectively neutralizes a variety of chemical agents including nerve gases and mustard [15]. Finally, medical facilities must consider environmental variables such as wind direction, wind velocity, temperature, and water runoff when setting up decontamination areas. These environmental considerations are important in protecting patients and employees from exposure to chemical agents, as well as minimizing the risk of contaminating buildings and equipment during the patient decontamination process.

Classification of Chemical Agents

Chemical agents are normally classified into broad categories based on their mechanisms of action and physiologic effects. The most common classification scheme divides them into the following categories:

Nerve agents
Vesicants
Cyanide agents or “blood” agents
Pulmonary agents or “choking” agents
Nonlethal incapacitating agents

Nerve Agents

Because they are the most toxic, nerve agents are the most feared of chemical agents. All nerve agents are organophosphorus compounds, which inhibit butyrylcholinesterase in the plasma, acetylcholinesterase in the red blood cell (RBC), and acetylcholinesterase at cholinergic receptor sites in the central and peripheral nervous systems. The chemical bond between nerve agent molecules and acetylcholinesterase is irreversible; thus, acetylcholinesterase activity returns only with new acetylcholinesterase synthesis or RBC turnover (1% per day) [16]. The decrease in acetylcholinesterase activity results in the accumulation of acetylcholine at both muscarinic and nicotinic
receptors in the central nervous system and neuromuscular junctions of the peripheral nervous system. Cholinergic overstimulation resulting from the accumulation of excess acetylcholine in the central and peripheral nervous systems is responsible for the clinical manifestations of nerve agent toxicity [17].

After an acute exposure to nerve agents, RBC acetylcholinesterase reflects nervous system acetylcholinesterase activity better than the activity of butyrylcholinesterase in the plasma. The measurement of RBC acetylcholinesterase activity is principally a research tool at the present time, and it is not useful in the management of mass casualties from nerve agent exposure. However, its measurement in blood samples collected from victims of a chemical attack may be useful in forensic investigations.

Several different nerve agents currently exist, each characterized by a unique molecular structure that irreversibly inhibits acetylcholinesterase. Compounds that were originally developed in Germany have been designated as the “G” series of nerves agents. The “V” series of agents are better absorbed through the skin than the “G” agents and are so designated because they are more “venomous.” The most common nerve agents include:

GA (tabun): ethyl N,N-dimethylphosphoramidocyanidate
GB (sarin): isopropyl methyl phosphonofluoridate
GD (soman): pinacolyl methyl phosphonofluoridate
GF: O-cyclohexyl-methylphosphonofluoridate
VX: O-ethyl S-(2-(diisopropylaminoethyl) methyl phosphonothiolate

The “G” agents are volatile, whereas VX is a persistent, oily substance with better percutaneous absorption. Each of these agents can be dispersed through a variety of weapons and munitions.

Inhalation of nerve gas is the most effective means of producing clinical effects, although it can also be ingested. High doses of persistent nerve agents, such as VX, can be absorbed through the skin. The clinical effects of nerve agent toxicity occur as a result of acetylcholine accumulating at both nicotinic sites (autonomic ganglia and skeletal muscle) as well as muscarinic sites (including postganglionic parasympathetic fibers, glands, and pulmonary and gastrointestinal smooth muscles). Nicotinic receptors appear to be most sensitive to the effects of nerve agents, with inactivation of acetylcholinesterase in autonomic ganglia and the neuromuscular junction of skeletal muscle responsible for many symptoms and signs of nerve agent exposure. The typical clinical manifestations of nerve agent toxicity are similar to those produced by organophosphate insecticides, although nerve agents are up to 1,000 times more toxic [17].

The basic clinical syndrome produced by nerve agents can be remembered by the acronym “SLUDGE”: salivation, lacrimation, urination, defecation, gastric distress, and emesis. Alternatively, “DUMBELS” (diarrhea, urination, miosis, bradycardia/bronchorrhea/bronchospasm, emesis, lacrimation, salivation/secretion/sweating) provides a more detailed tool to remember the muscarinic signs and symptoms [18]. Specific signs and symptoms in various organ systems depend on the dose of nerve agent received. Inhalation of a nerve agent usually produces immediate effects that occur within seconds to minutes after exposure. Dermal absorption usually produces delayed effects that can develop at any time between 10 minutes and 18 hours after skin exposure, depending on the dose. Common signs and symptoms in each organ system are summarized here.

Inhalation of a nerve agent typically results in the development of rhinorrhea, bronchorrhea, and bronchoconstriction soon after exposure. Dyspnea and chest tightness are common early symptoms. Coughing and wheezing may occur. The volume of airway secretions, the magnitude of bronchoconstriction, and the severity of airway symptoms all increase with higher exposure doses. High-dose or prolonged exposure may result in diaphragmatic weakness and centrally mediated apnea, which can result in ventilatory failure [16,17].

Although vagally mediated bradycardia is the expected heart rate response from cholinergic overstimulation of muscarinic receptors, this is commonly overridden by tachycardia resulting from nicotinic-mediated adrenergic stimulation and hypoxia. First-, second-, and third-degree heart block may occur [16,17]. Prolongation of the QTc interval can precipitate Torsade de pointes that has a poor prognosis [19]. Although hypertension may occur as a result of nicotinic-mediated adrenergic stimulation, blood pressure usually remains normal. A decline in blood pressure is typically a sign of impending death [4].

Muscarinic and nicotinic stimulation of the peripheral nervous system typically results in muscle fasciculations and profuse sweating, respectively. Muscle weakness and muscle paralysis may occur following high-dose exposures. Seizures can develop suddenly. The seizures may resolve spontaneously, but can be prolonged with status epilepticus [16,17]. Smaller-exposure doses typically result in nonspecific neurologic findings including an inability to concentrate, insomnia, irritability, and depression. A variety of psychological and behavioral changes, ranging from mild confusion to severe anxiety, can also occur [15]. Hallucinations or complete disorientation do not appear. Mild exposure also may result in a slight decline in memory function, as observed in first responders in the Tokyo sarin gas release of 1995 [20]. In the decade since that event, those exposed continue to have mild cerebellar effects and principally posttraumatic stress disorder [21].

Direct contact of the eyes with nerve agent vapor causes miosis that is usually associated with intense ocular pain. Patients also complain of blurred or dim vision and typically have injected conjunctivae with significant lacrimation.

Nausea and vomiting may be among the first signs of nerve agent toxicity. Abdominal cramping and diarrhea may also occur [16,17].

Unfortunately, few of the clinical signs or symptoms listed here may appear following exposure to a high dose of nerve agent. This is due to the fact that the range of exposure of doses, which produce clinical symptoms, is only slightly less than those which cause death. Therefore, central nervous system collapse with seizures, loss of consciousness, and central apnea may be the first signs of nerve agent toxicity following a high-dose exposure [16].

Management of all nerve agent casualties begins with the traditional “ABCs” of resuscitation: airway, breathing, and circulation support. Contaminated patients should be managed in the following order:

Airway management
Breathing support
Circulation and hemorrhage control
Antidote administration
Decontamination
Wound dressing
Evacuation to a noncontaminated treatment location [22]

Ventilatory failure is the primary cause of death following nerve agent exposure [23]. As a result, airway management and breathing support are extremely important in the management of nerve agent casualties. The nausea and vomiting that these patients typically experience must be considered in their airway management. In this regard, all patients should be considered to have a full stomach. Endotracheal intubation and assisted ventilation are required for the management of ventilatory failure. High airway resistance necessitating the need of pressures up to 50 to 70 cm of water may complicate ventilatory support [17]. Because of high airway pressures, if a cuffed endotracheal tube cannot be placed, a double-lumen Combitube (Tyco
Healthcare, Pleasanton, CA) is preferable to a laryngeal mask airway [24]. Once an effective airway has been established, ventilatory assistance can be provided by manual ventilation using a bag-valve device or by mechanical ventilation. Nebulized ipratropium can be used for the treatment of bronchospasm that may, in turn, result in decreased airway resistance [16]. Frequent suctioning is necessary to remove the copious airway secretions associated with nerve agent exposure. The use of depolarizing neuromuscular blocking agents during ventilatory assistance should be avoided [25].

The principal antidote for nerve agents is atropine. Atropine is an anticholinergic drug that blocks acetylcholine receptor sites. As a result, atropine blocks the pathophysiologic effects of the excess acetylcholine that accumulates as a result of nerve gas exposure; it is most effective at muscarinic sites. Atropine is primarily used for the purpose of drying up the copious airway secretions that patients develop following nerve agent exposure. The standard adult dosing regimen is 2 mg, administered intramuscularly, every 5 to 10 minutes, titrated to the patient’s secretions. The recommended pediatric dose is 0.05 mg per kg, with a minimum dose of 0.1 mg, administered intravenously every 2 to 5 minutes, titrated to effect [17,23]. In severe cases, adult patients may require 10 to 20 mg of atropine in the first hour to control secretions. The administration of atropine to a hypoxemic patient could precipitate the development of ventricular fibrillation. Therefore, oxygen should be administered and hypoxemia corrected before atropine is given [22,26]. Miosis will not respond to parenteral atropine. Topical tropicamide is effective for the treatment of miosis and the relief of ocular pain [23]. Atropine alone may not be an effective treatment for terminating seizures or reversing ventilatory failure [17,26]. Bulk atropine is available for reconstitution and may be required in the setting of mass nerve agent casualties.

Only gold members can continue reading. Log In or Register to continue